Safety And Efficacy Study Of Avelumab Plus Chemotherapy With Or Without Other Anti-Cancer Immunotherapy Agents In Patients With Advanced Malignancies
Sponsor
Pfizer (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03317496
Collaborator
(none)
67
46
4
57.2
1.5
0
Study Details
Study Description
Brief Summary
This is a Phase 1b/2, open label, multicenter, safety and clinical activity study of avelumab in combination with chemotherapy as first-line treatment of adult patients with locally advanced or metastatic solid tumors. Initially, avelumab will be evaluated in combination with pemetrexed and carboplatin in patients with advanced non-squamous non-small cell lung cancer (NSCLC) (Cohort A1) and in combination with gemcitabine and cisplatin in patients with cisplatin-eligible urothelial (bladder) cancer (UC) (Cohort A2). As more information is learned about other anti-cancer immunotherapy agents, in future portions of the study, avelumab may be combined with chemotherapy and other anti-cancer immunotherapy agents in patients with these same or different tumor types.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
This is a Phase 1b/2, open label, multicenter, safety, clinical activity, pharmacokinetic (PK), and pharmacodynamics (PD) study of avelumab in combination with chemotherapy with or without other anti-cancer immunotherapies, as first-line treatment of adult patients with locally advanced or metastatic solid tumors. Initially, avelumab will be evaluated in combination with pemetrexed and carboplatin in patients with advanced non-squamous non-small cell lung cancer (NSCLC) (Cohort A1) and with gemcitabine and cisplatin in patients with cisplatin-eligible urothelial cancer (UC) (Cohort A2).
Given the growing preclinical and clinical indications that combinations of anti-cancer immunotherapies potentially improve patient outcomes compared to results seen with single agents, in portions of the study to be added in the future, avelumab will be evaluated in combination with both standard-of-care chemotherapy and other anti-cancer immunotherapies in patients with advanced malignancies. Each cohort in the study will consist of a Phase 1b lead-in portion to evaluate safety and a Phase 2 cohort expansion to evaluate safety and efficacy.
In the Phase 1b safety lead-in portion, up to 12 patients will be enrolled into each cohort and evaluated for dose-limiting toxicities (DLT) during the first 2 cycles of treatment. If investigational products administration in a cohort is deemed safe in the Phase 1b lead-in, enrollment may be expanded into the Phase 2 cohort expansion. Up to approximately 40 patients in each cohort (including those enrolled in the Phase 1b lead-in and those enrolled in the Phase 2 cohort expansion) will be enrolled and treated with avelumab plus chemotherapy in the initial portion of the study and, in future portions of the study, with avelumab plus chemotherapy with or without other anti-cancer immunotherapies.
In the Phase 1b lead-in portions of NSCLC Cohort A1 and UC Cohort A2, avelumab is dosed at 800 mg fixed dose every 3 weeks. Under Protocol Amendment 4, avelumab is dosed at 1200 mg fixed dose every 3 weeks in the Phase 1b lead-in portions of NSCLC Cohort A3 and in UC Cohort A4, in combination with the same standard-of-care chemotherapy doublets used in Cohort A1 and Cohort A2, respectively. For each tumor type, the study treatment combination with the highest avelumab dose determined to be safe may be advanced into Phase 2 cohort expansion.
Study Design
Study Type:
Interventional
Actual Enrollment
:
67 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A MULTICENTER, OPEN-LABEL, PHASE 1B/2 STUDY TO EVALUATE SAFETY AND EFFICACY OF AVELUMAB (MSB0010718C) IN COMBINATION WITH CHEMOTHERAPY WITH OR WITHOUT OTHER ANTI-CANCER IMMUNOTHERAPIES AS FIRST-LINE TREATMENT IN PATIENTS WITH ADVANCED MALIGNANCIES
Actual Study Start Date
:
Dec 21, 2017
Actual Primary Completion Date
:
Jun 7, 2021
Anticipated Study Completion Date
:
Sep 28, 2022
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Group A Cohort A1 Non-squamous non-small cell lung cancer (NSCLC) patients treated with 800 mg avelumab plus pemetrexed/carboplatin |
Drug: Avelumab 800 mg in combination with pemetrexed / carboplatin
Avelumab Pemetrexed Carboplatin
|
| Experimental: Group A Cohort A2 Cisplatin-eligible urothelial cancer (UC)patients treated with 800 mg avelumab plus gemcitabine/cisplatin |
Drug: Avelumab 800 mg in combination with gemcitabine / cisplatin.
Avelumab Gemcitabine Cisplatin
|
| Experimental: Group A Cohort A3 Non-squamous non-small cell lung cancer (NSCLC) patients treated with 1200 mg avelumab plus pemetrexed/carboplatin |
Drug: Avelumab 1200 mg in combination with pemetrexed/carboplatin
Avelumab Pemetrexed Carboplatin
|
| Experimental: Group A Cohort A4 Cisplatin-eligible urothelial cancer (UC) patients treated with 1200 mg avelumab plus gemcitabine/cisplatin |
Drug: Avelumab 1200 mg in combination with gemcitabine/cisplatin
Avelumab Gemcitabine Cisplatin
|
Outcome Measures
Primary Outcome Measures
- Phase 1b Lead-in: Number of Participants With Dose-Limiting Toxicities (DLT) [Day 1 up to Week 6 (first 2 treatment cycles; 1 cycle = 21 days)]
DLTs=occurrence of any of the following AEs attributable to any study treatment in first 2 treatment cycles:Hematologic: grade(G)4 neutropenia lasting >7days;febrile neutropenia with body temperature >=38 degree Celsius for >1hour; G>=3 neutropenic infection(absolute neutrophil count <1.0*10^9/L),G>=3 thrombocytopenia (platelet count[PC] <50.0-25.0*10^9/L)with bleeding;G4 thrombocytopenia(PC<25.0*10^9/L),G4 anemia(life-threatening).Non-hematologic: any G4 toxicities;G3 toxicities persisting for >3days despite medical treatment(e.g.-nausea,vomiting,diarrhea)except endocrinopathies controlled with hormonal therapy;ALT/AST >3*upper limit of normal(ULN)if normal at baseline or 2*Baseline(>ULN at baseline)with total bilirubin >2*ULN and alkaline phosphatase <2*ULN;G3 QTcF prolongation after correction of any reversible cause(electrolyte abnormalities/hypoxia).Delay of >=3weeks in scheduled administration/failure to deliver 75% of doses due to toxicities attributable to any study treatment.
- Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment [From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 3.5 years approximately)]
OR defined as complete response(CR) or partial response(PR) as determined by investigator according to RECIST v1.1 from date of first dose of study treatment until date of first documentation of progressive disease(PD) and confirmed by repeat assessments performed no less than 4 weeks after first response. CR: disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, target and non-target must have short axis measures less than (<)10 millimeter(mm). PR: >=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD: >=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD.
Secondary Outcome Measures
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs [From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 3.5 years approximately)]
Adverse event (AE) was any untoward medical occurrence in a participant who received any study drug without regard to possibility of causal relationship. Serious adverse event was any untoward medical occurrence that at any dose resulted in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first.
- Number of Participants With Treatment Related TEAEs [From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 3.5 years approximately)]
A treatment related AE included AEs related to at least one study drug in the combination. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Relatedness to study drug was assessed by the investigator.
- Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v 4.03 [From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 3.5 years approximately)]
AE was any untoward medical occurrence in a participant who received any study drug without regard to possibility of causal relationship. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. TEAEs were graded by the investigator using NCI CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. In this outcome measure, number of participants with grade 3 or higher TEAEs were reported.
- Number of Participants With Laboratory Abnormalities by CTCAE Grade [From screening up to 90 days after last dose of study drug (maximum up to 3.5 years approximately)]
The number of participants with laboratory abnormalities of any Grade classified according to NCI CTCAE toxicity grading v4.03 were summarized: hematology (anemia, hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased and white blood cell decreased) and clinical chemistry (alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, cholesterol high, creatinine phosphokinase[cpk] increased, creatinine increased, gamma-glutamyl transferase[ggt] increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypertriglyceridemia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, serum amylase increased and lipase increased). As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
- Serum Concentration of Avelumab [Pre-dose, 1 hour post-dose on Day 1 of Cycle 1, 2, 3, 6, 10, 14; 336 hours post-dose on Day 15 of Cycle 1, 2, 3 (each cycle of 21 days)]
The lower limit of quantification (LLOQ) for avelumab was 0.2 micrograms per milliliter.
- Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies for Avelumab [From first dose of study drug up to last dose of study drug (maximum up to 3.5 years approximately)]
Blood samples were collected for assessment of avelumab ADAs using a tiered assay and confirmed positive samples were tested for neutralizing antibodies (nAb).
- Progression Free Survival (PFS) as Per RECIST v 1.1 by Investigator Assessment [From start of treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 3.5 years approximately)]
PFS was defined as the time from the date of first dose of study treatment to the date of the first documentation of PD per RECIST v1.1 or death due to any cause, whichever occurred first. PD = at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or appearance of one or more new lesions was considered progression.
- Overall Survival (OS) [From first dose of study treatment until death due to any cause (maximum up to 3.5 years approximately)]
OS was defined as the time from the first dose of study treatment to the date of death from any cause. Participants who were alive at the study end date or the last visit date available were censored at the date of last contact.
- Duration of Response (DOR) as Per RECIST v 1.1 by Investigator Assessment [From date of first documented response to date of first documented PD or death due to any cause, whichever occurred first (maximum up to 3.5 years approximately)]
DOR was defined as time from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of PD or death due to any cause, whichever occurs first. As per RECIST v1.1, CR = disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, both target and non-target must have short axis measures <10 mm. PR = at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD = at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or appearance of one or more new lesions was considered progression.
- Time-to-Tumor Response (TTR) as Per RECIST v 1.1 by Investigator Assessment [From first dose of study treatment until first documentation of CR or PR (maximum up to 3.5 years approximately)]
TTR was defined as the time from the date of first dose of study treatment to the first documentation of objective response (CR or PR) as assessed by investigator according to RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target and non-target lesions, with exception of nodal disease. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
- Absolute Value of Tumor Mutational Burden (TMB) in Tumor Tissue [Pre-dose on Day 1 of Cycle 1]
Mutational load within tumor tissue was defined as number per megabase of the genome, coding, base substitution, and indel mutations present in the sample. Mutational load was determined in whole blood samples using next generation deoxyribonucleic acid (DNA) sequencing followed by computational analysis.
- Number of Participants With Programmed Death-Ligand 1 (PD-L1) Expression [Baseline and Cycle 2 Day 8 (each cycle of 21 days)]
PD-L1 expression at was defined as the number of PD-L1 positive cells and/or qualitative assessment of PD-L1 staining on tumor and inflammatory cells in regions of interest. PD-L1 expression in the tumor was determined using immunohistochemistry. Participants were considered positive if their pretreatment tumor tissue sample demonstrated cell surface PD-L1 expression >=1% tumor cells or >= 5% immune cells and were otherwise considered negative. PD-L1 expression at baseline and on-treatment were reported in this outcome measure.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
- Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumor that is not amenable for treatment with curative intent as follows:
-
For all groups:
-
Measurable disease by RECIST v1.1 with at least 1 measurable lesion, and availability of tumor specimen 18 months or less old.
-
No prior systemic treatment for unresectable locally advanced or metastatic disease for the tumor type under study. If prior systemic chemotherapy treatment was given in the adjuvant or neo-adjuvant setting or as part of radiotherapy chemotherapy treatment, disease-free interval after stop of systemic treatment must be more than 6 months for non-squamous NSCLC and more than 12 months for UC;
-
Cohort A1 and Cohort A3: Non-squamous NSCLC, with no activating EGFR mutations, ALK or ROS1 translocations/rearrangements. If monotherapy pembrolizumab is available as a standard of care treatment option, patients must have a tumor proportion score (TPS) <50% for PD L1 (via the 22C3 pharmDx or the Ventana (SP263) PD L1 IHC assay).
-
Cohort A2 and Cohort A4: Transitional cell carcinoma of the urothelium including the bladder, urethra, renal pelvis, and ureter.
-
ECOG performance status 0 or 1
-
Estimated life expectancy of at least 90 days
-
Adequate bone marrow, renal, and liver function
-
Negative serum pregnancy test at screening
-
Signed and dated informed consent
Exclusion Criteria:
-
Prior immunotherapy with any antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways.
-
Patients with known symptomatic central nervous system metastases requiring steroids.
-
Diagnosis of other malignancy within 2 years prior to enrollment except adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the bladder, breast, or cervix, or low grade (Gleason ≤6) prostate cancer
-
Use of immunosuppressive medication at the time of enrollment
-
Active or prior autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent.
-
Prior organ transplantation including allogenic stem cell transplantation
-
Active infection requiring systemic therapy
-
Known history of HIV or AIDS
-
Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening
-
Administration of live vaccine within 4 weeks prior to study entry
-
Known prior severe hypersensitivity to the investigational products or any component in their formulations,
-
Known prior severe hypersensitivity to platinum-related compounds for all cohorts, to pemetrexed for patients enrolled in Cohort A1 and Cohort A3, and to gemcitabine for patients enrolled in Cohort A2 and Cohort A4
-
Persisting toxicity related to prior therapy (NCI CTCAE v4.03 Grade > 1)
-
Known history of colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis.
-
Ongoing cardiac dysrhythmias of NCI CTCAE v4.03 Grade 2 or prolongation of the QTcF interval to >480 msec.
-
Clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure, or serious cardiac arrhythmia requiring medication.
-
Major surgery ≤28 days or major radiation therapy ≤14 days prior to enrollment.
-
Participation in other studies involving investigational drug(s) within 28 days prior to study entry.
-
Concurrent treatment with a prohibited medication.
-
Other acute or chronic medical or psychiatric condition
-
Pregnant female patients; breastfeeding female patients; fertile male patients and female patients of childbearing potential who are unwilling or unable to use at least 1 highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 90 days after the last dose of chemotherapy (for male and female patients) or at least 30 days after the last dose of avelumab (for female patients), whichever is longer.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Arizona Cancer Center - North Campus | Tucson | Arizona | United States | 85719 |
| 2 | Banner-University Medical Center Tucson | Tucson | Arizona | United States | 85724 |
| 3 | Montefiore Medical Center - Einstein Center for Cancer Care | Bronx | New York | United States | 10461 |
| 4 | Montefiore Medical Center - Moses Division | Bronx | New York | United States | 10467 |
| 5 | Stony Brook Cancer Center | Stony Brook | New York | United States | 11794 |
| 6 | Stony Brook University | Stony Brook | New York | United States | 11794 |
| 7 | Duke University Medical Center/Duke Cancer Center | Durham | North Carolina | United States | 27710 |
| 8 | Investigational Chemotherapy Service | Durham | North Carolina | United States | 27710 |
| 9 | Chris O'Brien Lifehouse | Camperdown | New South Wales | Australia | 2050 |
| 10 | St Vincent's Hospital Sydney | Darlinghurst | New South Wales | Australia | 2010 |
| 11 | St Vincent's Public Hospital Sydney | Darlinghurst | New South Wales | Australia | 2010 |
| 12 | Western Health, Sunshine Hospital | St Albans | Victoria | Australia | 3021 |
| 13 | Kingston Health Sciences Centre - | Kingston | Ontario | Canada | K7L 2V7 |
| 14 | Fakultni nemocnice Olomouc, Klinika nuklearni mediciny | Olomouc | Czechia | 779 00 | |
| 15 | Fakultni nemocnice Olomouc, Ustav klinicke a molekularni patologie | Olomouc | Czechia | 779 00 | |
| 16 | Fakultni nemocnice Olomouc | Olomouc | Czechia | 779 00 | |
| 17 | Thomayerova nemocnice | Prague | Czechia | 140 59 | |
| 18 | Thomayerova nemocnice | Prague | Czechia | 14059 | |
| 19 | Centrum nuklearni mediciny s.r.o. | Prague | Czechia | 180 81 | |
| 20 | Centrum nuklearni mediciny s.r.o. | Prague | Czechia | 190 61 | |
| 21 | Vseobecna fakultni nemocnice v Praze | Praha 2 | Czechia | 120 00 | |
| 22 | Vseobecna fakultni nemocnice v Praze | Praha 2 | Czechia | 128 00 | |
| 23 | Vseobecna fakultni nemocnice v Praze | Praha 2 | Czechia | 128 08 | |
| 24 | Vseobecna fakultni nemocnice v Praze | Praha 2 | Czechia | 128 21 | |
| 25 | Orszagos Onkologiai Intezet "C" Belgyogyaszati - Onkologiai es Klinikai Farmakologiai Osztaly | Budapest | Hungary | 1122 | |
| 26 | AOU Ospedali Riuniti di Ancona Umberto I - GM Lancisi - G Salesi | Torrette Di Ancona | AN | Italy | 60126 |
| 27 | IRCCS Istit.Scient.Romagnolo per lo Studio e la Cura dei Tumori | Meldola | FC | Italy | 47014 |
| 28 | Centro di Ricerca di Fase 1, ASST Monza-Ospedale San Gerardo | Monza | MB | Italy | 20900 |
| 29 | Oncologia, ASST Monza-Ospedale San Gerardo | Monza | MB | Italy | 20900 |
| 30 | Istituto Europeo di Oncologia (IEO) | Milano | MI | Italy | 20141 |
| 31 | Istituto Nazionale Tumori di Napoli IRCCS Fondazione Pascale | Napoli | Italy | 80131 | |
| 32 | Hospital Universitario Vall d'Hebron | Barcelona | Spain | 08035 | |
| 33 | Hospital Clinic I Provincial | Barcelona | Spain | 08036 | |
| 34 | Hospital Universitario Fundacion Jimenez Diaz | Madrid | Spain | 28040 | |
| 35 | Hospital Universitario 12 de Octubre | Madrid | Spain | 28041 | |
| 36 | Fundacion Instituto Valenciano de Oncologia | Valencia | Spain | 46009 | |
| 37 | Royal Cornwall Hospital | Truro | Cornwall | United Kingdom | TR1 3LJ |
| 38 | The Platinum Medical Centre | London | England | United Kingdom | NW8 7JA |
| 39 | The Wellington Hospital - South | London | England | United Kingdom | NW8 9LE |
| 40 | Sarah Cannon Research Institute UK | London | England | United Kingdom | W1G 6AD |
| 41 | The Harley Street Clinic | London | England | United Kingdom | W1G 7LJ |
| 42 | HCA Pharmacy Department | London | England | United Kingdom | W1G 8HL |
| 43 | The Harley Street Clinic | London | England | United Kingdom | W1G 8PP |
| 44 | The Princess Grace Hospital | London | England | United Kingdom | W1U 5LZ |
| 45 | Weston Park Hospital | Sheffield | South Yorkshire | United Kingdom | S10 2SJ |
| 46 | Sir Bobby Robson Cancer Trials Research Centre | Newcastle upon Tyne | United Kingdom | NE7 7DN |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT03317496
Other Study ID Numbers:
- B9991023
- B9991023
- 2017-001741-27
- JAVELIN CHEMOTHERAPY MEDLEY
First Posted:
Oct 23, 2017
Last Update Posted:
Jun 23, 2022
Last Verified:
May 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The study was conducted in 2 phases: Phase 1b (lead-in phase) and Phase 2 (cohort expansion phase). Phase 2 was conducted at the highest dose level of avelumab which was determined safe for participants in Phase 1b. |
|---|---|
| Pre-assignment Detail | Phase 1b lead-in: 49 participants signed inform consent form (ICF). 18 participants did not meet eligibility criteria and were not enrolled. 31 participants enrolled and were assigned to study treatment. Phase 2: 52 participants signed ICF. 16 participants did not meet eligibility criteria and were not enrolled. 36 participants enrolled however 1 participant was not assigned to treatment. 35 participants were assigned to study treatment. |
| Arm/Group Title | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 1200 mg + Gemcitabine/Cisplatin | Phase 2: Avelumab 1200 mg + Gemcitabine/Cisplatin |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with advanced non-squamous non-small cell lung cancer (NSCLC) received avelumab 800 milligrams (mg) as an intravenous (IV) infusion over 1 hour every 3 weeks (Q3W) in combination with IV infusion of pemetrexed 500 milligram per square meter (mg/m^2) and carboplatin dose at area under curve (AUC) 5 (carboplatin dose [mg] = target AUC * glomerular filtration rate[GFR] milliliter per minute [mL/min] + 25, and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with urothelial cancer (UC) received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25), and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. |
| Period Title: Phase 1b Lead-in: Treatment | |||||
| STARTED | 6 | 13 | 6 | 6 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 6 | 13 | 6 | 6 | 0 |
| Period Title: Phase 1b Lead-in: Treatment | |||||
| STARTED | 4 | 11 | 5 | 4 | 0 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 4 | 11 | 5 | 4 | 0 |
| Period Title: Phase 1b Lead-in: Treatment | |||||
| STARTED | 0 | 0 | 0 | 0 | 35 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 35 |
| Period Title: Phase 1b Lead-in: Treatment | |||||
| STARTED | 0 | 0 | 0 | 0 | 25 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 25 |
Baseline Characteristics
| Arm/Group Title | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants with advanced NSCLC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25, and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25), and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm. | Total of all reporting groups |
| Overall Participants | 6 | 13 | 6 | 41 | 66 |
| Age (Years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [Years] |
69.67
(6.65)
|
63.00
(10.15)
|
64.67
(9.16)
|
65.24
(10.48)
|
65.15
(9.96)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
2
33.3%
|
5
38.5%
|
0
0%
|
10
24.4%
|
17
25.8%
|
| Male |
4
66.7%
|
8
61.5%
|
6
100%
|
31
75.6%
|
49
74.2%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
0
0%
|
1
7.7%
|
0
0%
|
0
0%
|
1
1.5%
|
| Not Hispanic or Latino |
6
100%
|
11
84.6%
|
6
100%
|
37
90.2%
|
60
90.9%
|
| Unknown or Not Reported |
0
0%
|
1
7.7%
|
0
0%
|
4
9.8%
|
5
7.6%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
7.7%
|
1
16.7%
|
1
2.4%
|
3
4.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
1
7.7%
|
0
0%
|
0
0%
|
1
1.5%
|
| White |
6
100%
|
11
84.6%
|
5
83.3%
|
37
90.2%
|
59
89.4%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
3
7.3%
|
3
4.5%
|
Outcome Measures
| Title | Phase 1b Lead-in: Number of Participants With Dose-Limiting Toxicities (DLT) |
|---|---|
| Description | DLTs=occurrence of any of the following AEs attributable to any study treatment in first 2 treatment cycles:Hematologic: grade(G)4 neutropenia lasting >7days;febrile neutropenia with body temperature >=38 degree Celsius for >1hour; G>=3 neutropenic infection(absolute neutrophil count <1.0*10^9/L),G>=3 thrombocytopenia (platelet count[PC] <50.0-25.0*10^9/L)with bleeding;G4 thrombocytopenia(PC<25.0*10^9/L),G4 anemia(life-threatening).Non-hematologic: any G4 toxicities;G3 toxicities persisting for >3days despite medical treatment(e.g.-nausea,vomiting,diarrhea)except endocrinopathies controlled with hormonal therapy;ALT/AST >3*upper limit of normal(ULN)if normal at baseline or 2*Baseline(>ULN at baseline)with total bilirubin >2*ULN and alkaline phosphatase <2*ULN;G3 QTcF prolongation after correction of any reversible cause(electrolyte abnormalities/hypoxia).Delay of >=3weeks in scheduled administration/failure to deliver 75% of doses due to toxicities attributable to any study treatment. |
| Time Frame | Day 1 up to Week 6 (first 2 treatment cycles; 1 cycle = 21 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| DLT-evaluable analysis set included all participants in phase 1b lead-in who were eligible for the study, received at least one dose of the combination treatment, and either experienced DLT or completed the DLT observation period during the first 2 cycles of treatment. |
| Arm/Group Title | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 1200 mg + Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Arm/Group Description | Participants with advanced NSCLC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25, and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25), and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. |
| Measure Participants | 6 | 12 | 6 | 6 |
| Count of Participants [Participants] |
0
0%
|
1
7.7%
|
0
0%
|
1
2.4%
|
| Title | Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment |
|---|---|
| Description | OR defined as complete response(CR) or partial response(PR) as determined by investigator according to RECIST v1.1 from date of first dose of study treatment until date of first documentation of progressive disease(PD) and confirmed by repeat assessments performed no less than 4 weeks after first response. CR: disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, target and non-target must have short axis measures less than (<)10 millimeter(mm). PR: >=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD: >=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD. |
| Time Frame | From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 3.5 years approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants who received at least 1 dose of any study drug. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan. |
| Arm/Group Title | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Arm/Group Description | Participants with advanced NSCLC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25, and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25), and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm. |
| Measure Participants | 6 | 13 | 6 | 41 |
| Number (95% Confidence Interval) [Percentage of participants] |
50.0
833.3%
|
53.8
413.8%
|
33.3
555%
|
39.0
95.1%
|
| Title | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs |
|---|---|
| Description | Adverse event (AE) was any untoward medical occurrence in a participant who received any study drug without regard to possibility of causal relationship. Serious adverse event was any untoward medical occurrence that at any dose resulted in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. |
| Time Frame | From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 3.5 years approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants who received at least 1 dose of any study drug. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan. |
| Arm/Group Title | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Arm/Group Description | Participants with advanced NSCLC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25, and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25), and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm. |
| Measure Participants | 6 | 13 | 6 | 41 |
| TEAEs |
6
100%
|
13
100%
|
6
100%
|
40
97.6%
|
| Serious TEAEs |
2
33.3%
|
9
69.2%
|
5
83.3%
|
20
48.8%
|
| Title | Number of Participants With Treatment Related TEAEs |
|---|---|
| Description | A treatment related AE included AEs related to at least one study drug in the combination. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. Relatedness to study drug was assessed by the investigator. |
| Time Frame | From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 3.5 years approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants who received at least 1 dose of any study drug. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan. |
| Arm/Group Title | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Arm/Group Description | Participants with advanced NSCLC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25, and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25), and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm. |
| Measure Participants | 6 | 13 | 6 | 41 |
| Count of Participants [Participants] |
6
100%
|
12
92.3%
|
6
100%
|
40
97.6%
|
| Title | Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v 4.03 |
|---|---|
| Description | AE was any untoward medical occurrence in a participant who received any study drug without regard to possibility of causal relationship. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. TEAEs were graded by the investigator using NCI CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. In this outcome measure, number of participants with grade 3 or higher TEAEs were reported. |
| Time Frame | From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 3.5 years approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety analysis set included all participants who received at least 1 dose of any study drug. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan. |
| Arm/Group Title | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Arm/Group Description | Participants with advanced NSCLC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25, and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25), and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm. |
| Measure Participants | 6 | 13 | 6 | 41 |
| Count of Participants [Participants] |
4
66.7%
|
12
92.3%
|
6
100%
|
36
87.8%
|
| Title | Number of Participants With Laboratory Abnormalities by CTCAE Grade |
|---|---|
| Description | The number of participants with laboratory abnormalities of any Grade classified according to NCI CTCAE toxicity grading v4.03 were summarized: hematology (anemia, hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased and white blood cell decreased) and clinical chemistry (alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, cholesterol high, creatinine phosphokinase[cpk] increased, creatinine increased, gamma-glutamyl transferase[ggt] increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypertriglyceridemia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, serum amylase increased and lipase increased). As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. |
| Time Frame | From screening up to 90 days after last dose of study drug (maximum up to 3.5 years approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Serum Concentration of Avelumab |
|---|---|
| Description | The lower limit of quantification (LLOQ) for avelumab was 0.2 micrograms per milliliter. |
| Time Frame | Pre-dose, 1 hour post-dose on Day 1 of Cycle 1, 2, 3, 6, 10, 14; 336 hours post-dose on Day 15 of Cycle 1, 2, 3 (each cycle of 21 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic concentration analysis set was subset of safety analysis set and included participants who had at least one concentration measurement for avelumab or other study drugs which they were assigned to receive. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan. Overall number of participants analyzed= participants evaluable for this outcome measure. Number analyzed= participants evaluable at specified time point. |
| Arm/Group Title | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Arm/Group Description | Participants with advanced NSCLC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25, and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25), and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm. |
| Measure Participants | 6 | 13 | 6 | 39 |
| Cycle 1/Day 1- pre-dose |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| Cycle 1/Day 1- 1 hour |
173300
(17)
|
180600
(14)
|
315100
(17)
|
306400
(22)
|
| Cycle 1/Day 15- 336 hours |
12320
(30)
|
9570
(55)
|
16510
(43)
|
14710
(46)
|
| Cycle 2/Day 1- pre-dose |
5331
(25)
|
3754
(67)
|
3856
(164)
|
5016
(96)
|
| Cycle 2/Day 1- 1 hour |
183300
(19)
|
197100
(13)
|
353000
(NA)
|
304400
(24)
|
| Cycle 2/Day 15- 336 hours |
16870
(16)
|
13550
(22)
|
13480
(78)
|
19000
(47)
|
| Cycle 3/Day 1- pre-dose |
8925
(25)
|
5651
(46)
|
4878
(205)
|
7542
(64)
|
| Cycle 3/Day 1- 1 hour |
122300
(5)
|
225600
(16)
|
59530
(692)
|
296800
(23)
|
| Cycle 3/Day 15- 336 hours |
19400
(9)
|
17150
(26)
|
26170
(46)
|
23510
(49)
|
| Cycle 6/Day 1- pre-dose |
11380
(16)
|
9518
(41)
|
10860
(88)
|
10140
(108)
|
| Cycle 6/Day 1- 1 hour |
174500
(13)
|
213600
(16)
|
237000
(NA)
|
344000
(18)
|
| Cycle 10/Day 1- pre-dose |
9523
(21)
|
8695
(66)
|
6620
(NA)
|
18550
(37)
|
| Cycle 10/Day 1- 1 hour |
179000
(25)
|
222000
(17)
|
6040
(NA)
|
242900
(69)
|
| Cycle 14/Day 1- pre-dose |
14970
(18)
|
13370
(47)
|
12240
(181)
|
16490
(36)
|
| Cycle 14/Day 1- 1 hour |
240200
(4)
|
216100
(18)
|
29050
(1005)
|
402200
(13)
|
| Title | Number of Participants With Positive Anti-Drug Antibody (ADA) and Neutralizing Antibodies for Avelumab |
|---|---|
| Description | Blood samples were collected for assessment of avelumab ADAs using a tiered assay and confirmed positive samples were tested for neutralizing antibodies (nAb). |
| Time Frame | From first dose of study drug up to last dose of study drug (maximum up to 3.5 years approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Progression Free Survival (PFS) as Per RECIST v 1.1 by Investigator Assessment |
|---|---|
| Description | PFS was defined as the time from the date of first dose of study treatment to the date of the first documentation of PD per RECIST v1.1 or death due to any cause, whichever occurred first. PD = at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or appearance of one or more new lesions was considered progression. |
| Time Frame | From start of treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 3.5 years approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Overall Survival (OS) |
|---|---|
| Description | OS was defined as the time from the first dose of study treatment to the date of death from any cause. Participants who were alive at the study end date or the last visit date available were censored at the date of last contact. |
| Time Frame | From first dose of study treatment until death due to any cause (maximum up to 3.5 years approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Duration of Response (DOR) as Per RECIST v 1.1 by Investigator Assessment |
|---|---|
| Description | DOR was defined as time from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of PD or death due to any cause, whichever occurs first. As per RECIST v1.1, CR = disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, both target and non-target must have short axis measures <10 mm. PR = at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD = at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm or appearance of one or more new lesions was considered progression. |
| Time Frame | From date of first documented response to date of first documented PD or death due to any cause, whichever occurred first (maximum up to 3.5 years approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants who received at least 1 dose of any study drug. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan. Here 'overall number of participants analyzed' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Arm/Group Description | Participants with advanced NSCLC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25, and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25), and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm. |
| Measure Participants | 3 | 7 | 2 | 16 |
| Median (95% Confidence Interval) [Months] |
NA
|
9.6
|
4.4
|
6.6
|
| Title | Time-to-Tumor Response (TTR) as Per RECIST v 1.1 by Investigator Assessment |
|---|---|
| Description | TTR was defined as the time from the date of first dose of study treatment to the first documentation of objective response (CR or PR) as assessed by investigator according to RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target and non-target lesions, with exception of nodal disease. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Time Frame | From first dose of study treatment until first documentation of CR or PR (maximum up to 3.5 years approximately) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants who received at least 1 dose of any study drug. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan. Here 'overall number of participants analyzed' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Arm/Group Description | Participants with advanced NSCLC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25, and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25), and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm. |
| Measure Participants | 3 | 7 | 2 | 16 |
| Median (Full Range) [Months] |
2.8
|
1.4
|
1.3
|
1.5
|
| Title | Absolute Value of Tumor Mutational Burden (TMB) in Tumor Tissue |
|---|---|
| Description | Mutational load within tumor tissue was defined as number per megabase of the genome, coding, base substitution, and indel mutations present in the sample. Mutational load was determined in whole blood samples using next generation deoxyribonucleic acid (DNA) sequencing followed by computational analysis. |
| Time Frame | Pre-dose on Day 1 of Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The tumor tissue based biomarker analysis set was subset of the safety analysis set and included participants who had at least one baseline and one on-treatment biomarker assessment for the same biomarker. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan. |
| Arm/Group Title | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Arm/Group Description | Participants with advanced NSCLC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25, and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25), and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm. |
| Measure Participants | 4 | 13 | 5 | 39 |
| Mean (Standard Deviation) [Mutations per megabase] |
4.345
(6.7533)
|
2.774
(2.7594)
|
4.442
(5.1517)
|
2.468
(2.8828)
|
| Title | Number of Participants With Programmed Death-Ligand 1 (PD-L1) Expression |
|---|---|
| Description | PD-L1 expression at was defined as the number of PD-L1 positive cells and/or qualitative assessment of PD-L1 staining on tumor and inflammatory cells in regions of interest. PD-L1 expression in the tumor was determined using immunohistochemistry. Participants were considered positive if their pretreatment tumor tissue sample demonstrated cell surface PD-L1 expression >=1% tumor cells or >= 5% immune cells and were otherwise considered negative. PD-L1 expression at baseline and on-treatment were reported in this outcome measure. |
| Time Frame | Baseline and Cycle 2 Day 8 (each cycle of 21 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS included all participants who received at least one dose of study drug. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan. |
| Arm/Group Title | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin |
|---|---|---|---|---|
| Arm/Group Description | Participants with advanced NSCLC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25, and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25), and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm. |
| Measure Participants | 6 | 13 | 6 | 41 |
| Baseline- Positive PD-L1 |
0
0%
|
6
46.2%
|
1
16.7%
|
28
68.3%
|
| Baseline- Negative PD-L1 |
4
66.7%
|
7
53.8%
|
4
66.7%
|
13
31.7%
|
| Baseline- Unknown PD-L1 |
2
33.3%
|
0
0%
|
1
16.7%
|
0
0%
|
| On-treatment (Cycle 2 Day 8)- Positive PD-L1 |
0
0%
|
2
15.4%
|
1
16.7%
|
3
7.3%
|
| On-treatment (Cycle 2 Day 8)- Negative PD-L1 |
2
33.3%
|
1
7.7%
|
0
0%
|
6
14.6%
|
| On-treatment (Cycle 2 Day 8)- Unknown PD-L1 |
4
66.7%
|
10
76.9%
|
5
83.3%
|
32
78%
|
Adverse Events
| Time Frame | All-cause mortality: From start of the treatment up to 90 days post last dose of study treatment (maximum of 3.5 years approximately), TEAEs and Serious TEAEs: From start of the treatment up to 30 days post last dose of study treatment (maximum of 3.5 years approximately) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Same event may appear as both an AE and SAE. However, what is presented are distinct events. Safety set was evaluated. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan. TEAEs: events with onset dates occurring during on-treatment period (time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first). | |||||||
| Arm/Group Title | Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin | ||||
| Arm/Group Description | Participants with advanced NSCLC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25, and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 800 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants with advanced NSCLC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV infusion of pemetrexed 500 mg/m^2 and carboplatin dose at AUC 5 (carboplatin dose [mg] = target AUC * GFR mL/min + 25), and maximum carboplatin dose = target AUC [mg*min/mL] * 150 mL/min) on Day 1 of each 21-day cycle. Pemetrexed/carboplatin were administered for a maximum of 4 to 6 cycles. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. | Participants (cisplatin-eligible) with UC received avelumab 1200 mg as an IV infusion over 1 hour Q3W in combination with IV administration of cisplatin 70 mg/m^2 and gemcitabine 1000 mg/m^2 on Day 1 of each 21-day cycle with gemcitabine being administered on Day 1 and Day 8. Safety follow-up was for 90 days after last dose of study treatment or until time of initiation of new anticancer treatment, whichever comes first. Participants from both Phase 1b and Phase 2 Avelumab 1200 mg + Gemcitabine/Cisplatin were included in this arm. | ||||
All Cause Mortality |
||||||||
| Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/6 (33.3%) | 7/13 (53.8%) | 5/6 (83.3%) | 22/41 (53.7%) | ||||
Serious Adverse Events |
||||||||
| Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/6 (33.3%) | 9/13 (69.2%) | 5/6 (83.3%) | 20/41 (48.8%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Pancytopenia | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Cardiac disorders | ||||||||
| Atrial thrombosis | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Atrioventricular block | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Bradycardia | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Cardiomyopathy | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Myocardial infarction | 0/6 (0%) | 2/13 (15.4%) | 0/6 (0%) | 0/41 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Colitis | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Constipation | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Diarrhoea | 1/6 (16.7%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Ileus | 0/6 (0%) | 0/13 (0%) | 1/6 (16.7%) | 0/41 (0%) | ||||
| Nausea | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Pancreatitis | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Small intestinal obstruction | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Subileus | 0/6 (0%) | 0/13 (0%) | 1/6 (16.7%) | 0/41 (0%) | ||||
| Vomiting | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| General disorders | ||||||||
| Malaise | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Sudden death | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Hepatobiliary disorders | ||||||||
| Autoimmune hepatitis | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Infections and infestations | ||||||||
| Bacteraemia | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Bacteriuria | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Infection | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Pyelonephritis | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Rectal abscess | 0/6 (0%) | 0/13 (0%) | 1/6 (16.7%) | 0/41 (0%) | ||||
| Rhinovirus infection | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Sepsis | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Urinary tract infection | 0/6 (0%) | 2/13 (15.4%) | 0/6 (0%) | 4/41 (9.8%) | ||||
| Urosepsis | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Humerus fracture | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Infusion related reaction | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 2/41 (4.9%) | ||||
| Spinal fracture | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Thoracic vertebral fracture | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Aspartate aminotransferase increased | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hyperkalaemia | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Back pain | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Fasciitis | 0/6 (0%) | 0/13 (0%) | 1/6 (16.7%) | 0/41 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Neoplasm progression | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Nervous system disorders | ||||||||
| Cerebrovascular accident | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Hydrocephalus | 0/6 (0%) | 0/13 (0%) | 1/6 (16.7%) | 0/41 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 1/6 (16.7%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Renal impairment | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Urinary retention | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Haemoptysis | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Interstitial lung disease | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Pneumonitis | 0/6 (0%) | 0/13 (0%) | 2/6 (33.3%) | 0/41 (0%) | ||||
| Pneumothorax | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Pulmonary embolism | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Vascular disorders | ||||||||
| Hypotension | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Peripheral embolism | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin | Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin | Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin | Phase 1b and 2: Avelumab 1200 mg + Gemcitabine/Cisplatin | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/6 (100%) | 13/13 (100%) | 6/6 (100%) | 40/41 (97.6%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 3/6 (50%) | 10/13 (76.9%) | 1/6 (16.7%) | 26/41 (63.4%) | ||||
| Haemolytic anaemia | 0/6 (0%) | 0/13 (0%) | 1/6 (16.7%) | 0/41 (0%) | ||||
| Leukopenia | 0/6 (0%) | 2/13 (15.4%) | 0/6 (0%) | 6/41 (14.6%) | ||||
| Lymphopenia | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Neutropenia | 3/6 (50%) | 8/13 (61.5%) | 4/6 (66.7%) | 23/41 (56.1%) | ||||
| Thrombocytopenia | 0/6 (0%) | 4/13 (30.8%) | 4/6 (66.7%) | 20/41 (48.8%) | ||||
| Thrombocytosis | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Cardiac disorders | ||||||||
| Atrial fibrillation | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Intracardiac thrombus | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Palpitations | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Sinus bradycardia | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Tachycardia | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Ear and labyrinth disorders | ||||||||
| Tinnitus | 0/6 (0%) | 2/13 (15.4%) | 0/6 (0%) | 4/41 (9.8%) | ||||
| Endocrine disorders | ||||||||
| Hyperthyroidism | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Hypophysitis | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Hypothyroidism | 1/6 (16.7%) | 1/13 (7.7%) | 1/6 (16.7%) | 1/41 (2.4%) | ||||
| Eye disorders | ||||||||
| Conjunctival haemorrhage | 0/6 (0%) | 0/13 (0%) | 1/6 (16.7%) | 0/41 (0%) | ||||
| Dry eye | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Abdominal distension | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Abdominal pain | 2/6 (33.3%) | 4/13 (30.8%) | 0/6 (0%) | 3/41 (7.3%) | ||||
| Abdominal pain upper | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 3/41 (7.3%) | ||||
| Abdominal rigidity | 0/6 (0%) | 0/13 (0%) | 1/6 (16.7%) | 0/41 (0%) | ||||
| Ascites | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Constipation | 0/6 (0%) | 4/13 (30.8%) | 1/6 (16.7%) | 16/41 (39%) | ||||
| Diarrhoea | 2/6 (33.3%) | 4/13 (30.8%) | 3/6 (50%) | 7/41 (17.1%) | ||||
| Dry mouth | 1/6 (16.7%) | 2/13 (15.4%) | 0/6 (0%) | 2/41 (4.9%) | ||||
| Dyspepsia | 0/6 (0%) | 4/13 (30.8%) | 0/6 (0%) | 2/41 (4.9%) | ||||
| Gastritis | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Gastrointestinal disorder | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Gastrooesophageal reflux disease | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 5/41 (12.2%) | ||||
| Glossodynia | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Haemorrhoidal haemorrhage | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Lip dry | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Melaena | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Nausea | 3/6 (50%) | 9/13 (69.2%) | 4/6 (66.7%) | 19/41 (46.3%) | ||||
| Oral disorder | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Pancreatic failure | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Stomatitis | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 2/41 (4.9%) | ||||
| Vomiting | 1/6 (16.7%) | 5/13 (38.5%) | 1/6 (16.7%) | 14/41 (34.1%) | ||||
| General disorders | ||||||||
| Asthenia | 2/6 (33.3%) | 2/13 (15.4%) | 0/6 (0%) | 11/41 (26.8%) | ||||
| Chest pain | 1/6 (16.7%) | 0/13 (0%) | 1/6 (16.7%) | 0/41 (0%) | ||||
| Discomfort | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Extravasation | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Fatigue | 3/6 (50%) | 8/13 (61.5%) | 3/6 (50%) | 14/41 (34.1%) | ||||
| Influenza like illness | 1/6 (16.7%) | 2/13 (15.4%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Mucosal inflammation | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Oedema peripheral | 0/6 (0%) | 2/13 (15.4%) | 0/6 (0%) | 3/41 (7.3%) | ||||
| Pain | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 2/41 (4.9%) | ||||
| Pyrexia | 2/6 (33.3%) | 1/13 (7.7%) | 0/6 (0%) | 11/41 (26.8%) | ||||
| Thirst | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Hepatitis | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Immune system disorders | ||||||||
| Cytokine release syndrome | 0/6 (0%) | 0/13 (0%) | 1/6 (16.7%) | 0/41 (0%) | ||||
| Infections and infestations | ||||||||
| Candida infection | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Cellulitis | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Clostridium difficile infection | 0/6 (0%) | 0/13 (0%) | 1/6 (16.7%) | 0/41 (0%) | ||||
| Conjunctivitis | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Herpes zoster | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Localised infection | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Mucosal infection | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Nasopharyngitis | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Oral candidiasis | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Oral herpes | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Pneumonia | 0/6 (0%) | 0/13 (0%) | 1/6 (16.7%) | 0/41 (0%) | ||||
| Sepsis | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Upper respiratory tract infection | 2/6 (33.3%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Urinary tract infection | 1/6 (16.7%) | 1/13 (7.7%) | 1/6 (16.7%) | 6/41 (14.6%) | ||||
| Urosepsis | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Viral upper respiratory tract infection | 0/6 (0%) | 0/13 (0%) | 1/6 (16.7%) | 0/41 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Back injury | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Contusion | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 2/41 (4.9%) | ||||
| Fall | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 2/41 (4.9%) | ||||
| Femur fracture | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Infusion related reaction | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Pelvic fracture | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Procedural pneumothorax | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Skin abrasion | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Urinary tract stoma complication | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 2/6 (33.3%) | 1/13 (7.7%) | 1/6 (16.7%) | 13/41 (31.7%) | ||||
| Amylase increased | 2/6 (33.3%) | 2/13 (15.4%) | 0/6 (0%) | 2/41 (4.9%) | ||||
| Aspartate aminotransferase increased | 2/6 (33.3%) | 2/13 (15.4%) | 0/6 (0%) | 9/41 (22%) | ||||
| Blood alkaline phosphatase increased | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 8/41 (19.5%) | ||||
| Blood bilirubin increased | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 2/41 (4.9%) | ||||
| Blood calcium increased | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Blood cholesterol increased | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 2/41 (4.9%) | ||||
| Blood creatinine increased | 3/6 (50%) | 2/13 (15.4%) | 0/6 (0%) | 13/41 (31.7%) | ||||
| Blood pressure increased | 0/6 (0%) | 2/13 (15.4%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Blood thyroid stimulating hormone increased | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Blood triglycerides increased | 0/6 (0%) | 2/13 (15.4%) | 0/6 (0%) | 0/41 (0%) | ||||
| Body temperature increased | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Gamma-glutamyltransferase increased | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 7/41 (17.1%) | ||||
| Haemoglobin decreased | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 3/41 (7.3%) | ||||
| Lipase increased | 0/6 (0%) | 2/13 (15.4%) | 1/6 (16.7%) | 1/41 (2.4%) | ||||
| Lymphocyte count decreased | 0/6 (0%) | 3/13 (23.1%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Neutrophil count decreased | 0/6 (0%) | 3/13 (23.1%) | 0/6 (0%) | 5/41 (12.2%) | ||||
| Platelet count decreased | 4/6 (66.7%) | 4/13 (30.8%) | 1/6 (16.7%) | 9/41 (22%) | ||||
| Prothrombin time prolonged | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Transaminases increased | 1/6 (16.7%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Troponin increased | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Weight decreased | 0/6 (0%) | 2/13 (15.4%) | 2/6 (33.3%) | 6/41 (14.6%) | ||||
| White blood cell count decreased | 2/6 (33.3%) | 3/13 (23.1%) | 0/6 (0%) | 6/41 (14.6%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 2/6 (33.3%) | 3/13 (23.1%) | 1/6 (16.7%) | 10/41 (24.4%) | ||||
| Hypercalcaemia | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 2/41 (4.9%) | ||||
| Hyperglycaemia | 1/6 (16.7%) | 1/13 (7.7%) | 0/6 (0%) | 3/41 (7.3%) | ||||
| Hyperkalaemia | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 2/41 (4.9%) | ||||
| Hypertriglyceridaemia | 1/6 (16.7%) | 1/13 (7.7%) | 0/6 (0%) | 3/41 (7.3%) | ||||
| Hyperuricaemia | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Hypoalbuminaemia | 0/6 (0%) | 2/13 (15.4%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Hypocalcaemia | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 2/41 (4.9%) | ||||
| Hypochloraemia | 1/6 (16.7%) | 0/13 (0%) | 1/6 (16.7%) | 0/41 (0%) | ||||
| Hypokalaemia | 2/6 (33.3%) | 1/13 (7.7%) | 0/6 (0%) | 5/41 (12.2%) | ||||
| Hypomagnesaemia | 2/6 (33.3%) | 2/13 (15.4%) | 0/6 (0%) | 4/41 (9.8%) | ||||
| Hyponatraemia | 0/6 (0%) | 2/13 (15.4%) | 1/6 (16.7%) | 3/41 (7.3%) | ||||
| Hypophosphataemia | 3/6 (50%) | 0/13 (0%) | 0/6 (0%) | 2/41 (4.9%) | ||||
| Increased appetite | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 2/6 (33.3%) | 2/13 (15.4%) | 1/6 (16.7%) | 8/41 (19.5%) | ||||
| Back pain | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 6/41 (14.6%) | ||||
| Chondropathy | 0/6 (0%) | 2/13 (15.4%) | 0/6 (0%) | 0/41 (0%) | ||||
| Clubbing | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Groin pain | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Muscle spasms | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Muscular weakness | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Musculoskeletal chest pain | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Musculoskeletal pain | 0/6 (0%) | 0/13 (0%) | 1/6 (16.7%) | 0/41 (0%) | ||||
| Myalgia | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Myositis | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Osteolysis | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Spinal pain | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Flank pain | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 3/41 (7.3%) | ||||
| Nervous system disorders | ||||||||
| Ataxia | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Cognitive disorder | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Dizziness | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 5/41 (12.2%) | ||||
| Dizziness postural | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Dysgeusia | 1/6 (16.7%) | 2/13 (15.4%) | 0/6 (0%) | 5/41 (12.2%) | ||||
| Headache | 1/6 (16.7%) | 1/13 (7.7%) | 1/6 (16.7%) | 2/41 (4.9%) | ||||
| Hypoaesthesia | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 2/41 (4.9%) | ||||
| Lethargy | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Neuralgia | 0/6 (0%) | 0/13 (0%) | 1/6 (16.7%) | 1/41 (2.4%) | ||||
| Neuropathy peripheral | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 3/41 (7.3%) | ||||
| Presyncope | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Sciatica | 1/6 (16.7%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Taste disorder | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Tremor | 1/6 (16.7%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Psychiatric disorders | ||||||||
| Agitation | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Depression | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 3/41 (7.3%) | ||||
| Insomnia | 2/6 (33.3%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Irritability | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Mood altered | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Renal and urinary disorders | ||||||||
| Acute kidney injury | 0/6 (0%) | 2/13 (15.4%) | 0/6 (0%) | 3/41 (7.3%) | ||||
| Chronic kidney disease | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Genitourinary symptom | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Haematuria | 0/6 (0%) | 3/13 (23.1%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Polyuria | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Renal impairment | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Urine odour abnormal | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Pelvic pain | 0/6 (0%) | 0/13 (0%) | 1/6 (16.7%) | 0/41 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 0/6 (0%) | 1/13 (7.7%) | 1/6 (16.7%) | 3/41 (7.3%) | ||||
| Dyspnoea | 2/6 (33.3%) | 1/13 (7.7%) | 2/6 (33.3%) | 5/41 (12.2%) | ||||
| Dyspnoea exertional | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Epistaxis | 0/6 (0%) | 0/13 (0%) | 1/6 (16.7%) | 1/41 (2.4%) | ||||
| Haemoptysis | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Hypoxia | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Pneumonitis | 2/6 (33.3%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Productive cough | 0/6 (0%) | 1/13 (7.7%) | 1/6 (16.7%) | 0/41 (0%) | ||||
| Pulmonary embolism | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 4/41 (9.8%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 0/6 (0%) | 2/13 (15.4%) | 0/6 (0%) | 0/41 (0%) | ||||
| Dermal cyst | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Dermatitis | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Dry skin | 1/6 (16.7%) | 1/13 (7.7%) | 1/6 (16.7%) | 2/41 (4.9%) | ||||
| Erythema | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Hyperhidrosis | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Pruritus | 2/6 (33.3%) | 1/13 (7.7%) | 0/6 (0%) | 4/41 (9.8%) | ||||
| Psoriasis | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Rash | 1/6 (16.7%) | 3/13 (23.1%) | 1/6 (16.7%) | 5/41 (12.2%) | ||||
| Rash pruritic | 1/6 (16.7%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
| Skin exfoliation | 1/6 (16.7%) | 0/13 (0%) | 0/6 (0%) | 0/41 (0%) | ||||
| Vascular disorders | ||||||||
| Deep vein thrombosis | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 2/41 (4.9%) | ||||
| Hypertension | 0/6 (0%) | 0/13 (0%) | 0/6 (0%) | 4/41 (9.8%) | ||||
| Lymphoedema | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Superficial vein thrombosis | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 1/41 (2.4%) | ||||
| Thrombosis | 0/6 (0%) | 1/13 (7.7%) | 0/6 (0%) | 0/41 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT03317496
Other Study ID Numbers:
- B9991023
- B9991023
- 2017-001741-27
- JAVELIN CHEMOTHERAPY MEDLEY
First Posted:
Oct 23, 2017
Last Update Posted:
Jun 23, 2022
Last Verified:
May 1, 2022