PDR001 Plus LAG525 for Patients With Advanced Solid and Hematologic Malignancies
Study Details
Study Description
Brief Summary
The purpose of this signal seeking study is to determine whether treatment with PDR001 and LAG525 demonstrates sufficient efficacy in advanced malignancies to warrant further study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This was a phase II, open-label study to determine the efficacy and safety of treatment with the combination of PDR001+LAG525 across multiple tumor types that are relapsed and/or refractory to available standard of care therapies. There were 7 tumor cohorts assessed: 1) Small cell lung cancer, 2) Gastric/esophageal adenocarcinoma, 3) Castration resistant prostate adenocarcinoma (CRPC), 4) Soft tissue sarcoma, 5) Ovarian adenocarcinoma, 6) Advanced well-differentiated neuroendocrine tumors and 7) Diffuse large B cell lymphoma (DLBCL).
Participants were treated with the combination of PDR001 300 mg with LAG525 400 mg once every 3 weeks (Q3W) via intravenous (i.v.) infusion. Participants received study treatment for a maximum of 2 years, or until disease progression (assessed by investigator per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) or the Revised Response Criteria for Malignant Lymphoma criteria (Cheson et al 2007)), unacceptable toxicity, death or discontinuation from study treatment for any other reason.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PDR001+LAG525 PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001. |
Biological: PDR001
PDR001 is a high-affinity, ligand-blocking, humanized anti-programmed death-1 (PD-1) IgG4 antibody that blocks the binding of Programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2) to PD-1.
Biological: LAG525
LAG525 is a high-affinity, ligand-blocking, humanized anti-LAG-3 IgG4 antibody which blocks the binding of the known LAG-3 ligand MHC class II to LAG-3.
|
Outcome Measures
Primary Outcome Measures
- Clinical Benefit Rate (CBR) at 24 Weeks of PDR001+LAG525 by Tumor Type in Multiple Solid Tumors and Lymphoma [24 weeks]
CBR is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) and Stable Disease (SD). Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression. CBR (CR+PR+SD) is reported overall and by tumor type.
Secondary Outcome Measures
- Overall Response Rate (ORR) [From start of treatment until end of treatment, assessed up to 113 weeks]
ORR is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. ORR (CR+PR) is reported overall (including all tumor types).
- Time to Response (TTR) [From start of treatment to the first documented response of either complete response or partial response, assessed up to 113 weeks]
TTR is defined as the time from the date of first dose to the date of first documented response of Complete Response (CR) or Partial Response (PR). In case of solid tumor if a patient did not achieve a confirmed response they were censored at maximum follow-up for patients who had a PFS event (progressed or died due to any cause), or at last adequate tumor assessment date otherwise. Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007).
- Duration of Response (DOR) [From first documented response (CR or PR) to first documented progression or death, assessed up to 113 weeks]
DOR only applies to subjects for whom best overall response is complete response (CR) or partial response (PR). DOR is defined as the time between the date of first documented response (CR or PR) and the date of first documented progression/relapse or death due to any cause within 150 days of the last study drug dose date. If a patient not had an event, duration was censored at the date of last adequate tumor assessment. Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007).
- Time to Progression (TTP) [From start of treatment to first documented progression or death due to underlying cancer, assessed up to 113 weeks]
TTP is the time from start of treatment to the date of event defined as the first documented progression or death due to underlying cancer. If a patient not had an event, time to progression was censored at the date of last adequate tumor assessment. Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007).
- Progression-Free Survival (PFS) [From start of treatment to first documented progression or death, assessed up to 113 weeks]
PFS is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause within 150 days of the last dose. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007).
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [From first dose of study treatment until last dose of study treatment plus 150 days post treatment, assessed up to 135 weeks.]
Number of participants with AEs and SAEs including changes in laboratory parameters, vital signs and ECGs qualifying and reported as AEs.
- Number of Participants With Dose Interruptions and Permanent Discontinuation of Study Drug [From first dose of study treatment until last dose of study treatment, assessed up to 113 weeks.]
Number of participants with at least one dose interruption of PDR001 and LAG525 and number of participants with permanent dose discontinuation of PDR001 and LAG525.
- Dose Intensity [From first dose of study treatment until last dose of study treatment, assessed up to 113 weeks.]
Dose intensity (mg/day) of PDR001 and LAG525 is calculated as cumulative dose in milligrams divided by duration of exposure in days.
Eligibility Criteria
Criteria
Inclusion Criteria:
Patients eligible for inclusion in this study had to meet all of the following criteria:
-
Patient must have had at least one prior line of therapy for their disease and must not be beyond 4th progression/relapse of disease (5 maximum prior lines).
-
Patient has a pathology confirmed diagnosis of a solid tumor or lymphoma listed in the section "condition". Patients must have measurable disease as per appropriate guidelines (Solid Tumors by RECIST 1.1 and Diffuse Large B-cell Lymphoma by Revised Response Criteria for Malignant Lymphoma - Cheson et al 2007).
Exclusion Criteria:
Patients eligible for this study must not meet any of the following criteria:
-
History of severe hypersensitivity reactions to other monoclonal antibodies.
-
Impaired cardiac function or clinically significant cardiac disease.
-
Active, known or suspected autoimmune disease or a documented history of autoimmune disease within three years prior to screening with a few exceptions as per protocol.
-
Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.
-
Patient with second primary malignancy within < 3 years of first dose of study treatment.
-
Prior immunotherapy treatment with PD-1, PD-L1, CTLA-4, or LAG-3 antibodies.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | California Pacific Medical Center Drug Shipment (2) | San Francisco | California | United States | 94120-7999 |
| 2 | Hematology Oncology Associates of the Treasure Coast | Port Saint Lucie | Florida | United States | 34952 |
| 3 | University Cancer and Blood Center, LLC | Athens | Georgia | United States | 30607 |
| 4 | Northwestern University Medical School | Chicago | Illinois | United States | 60611 |
| 5 | University of Illinois Cancer Center at Chicago SC | Chicago | Illinois | United States | 60612 |
| 6 | Illinois Cancer Care P.C. Jesse Brown VA | Peoria | Illinois | United States | 61615-7828 |
| 7 | Indiana University | Indianapolis | Indiana | United States | 46202 |
| 8 | University of Iowa Hospitals and Clinics Comprehensive Cancer Center | Iowa City | Iowa | United States | 52242 |
| 9 | The University of Kansas Clinical Research Center | Fairway | Kansas | United States | 66205 |
| 10 | Weinberg Cancer Institute at Franklin Square Hospital | Baltimore | Maryland | United States | 21237-3998 |
| 11 | Billings Clinic Dept of Billings Clinic(2) | Billings | Montana | United States | 59101 |
| 12 | Oncology Hematology West Nebraska Cancer Specialists | Omaha | Nebraska | United States | 68124 |
| 13 | Comprehensive Cancer Centers | Las Vegas | Nevada | United States | 89169 |
| 14 | Oregon Health and Science University | Portland | Oregon | United States | 97239 |
| 15 | Oncology Consultants Oncology Consultants | Houston | Texas | United States | 77024 |
| 16 | University of Texas - MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 17 | Kadlec Clinic Hematology and Oncology | Kennewick | Washington | United States | 99336 |
| 18 | Providence Regional Cancer System SC | Lacey | Washington | United States | 98503 |
| 19 | University of Wisconsin Hospital and Clinics | Madison | Wisconsin | United States | 53792 |
| 20 | Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- CPDR001XUS01
Study Results
Participant Flow
| Recruitment Details | Participants took part in 20 investigative sites in 1 country (United States). |
|---|---|
| Pre-assignment Detail | The screening period began once patients had signed the study informed consent. All screening evaluations were performed as closely as possible to the beginning of treatment and never more than 21 days prior to starting study treatment. After screening, the treatment period started on Cycle 1 Day 1. |
| Arm/Group Title | PDR001+LAG525 |
|---|---|
| Arm/Group Description | PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001. |
| Period Title: Overall Study | |
| STARTED | 76 |
| Full Analysis Set (FAS) | 75 |
| COMPLETED | 4 |
| NOT COMPLETED | 72 |
Baseline Characteristics
| Arm/Group Title | PDR001+LAG525 |
|---|---|
| Arm/Group Description | PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001. |
| Overall Participants | 76 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
65.1
(10.57)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
31
40.8%
|
| Male |
45
59.2%
|
| Race/Ethnicity, Customized (Count of Participants) | |
| Asian |
1
1.3%
|
| Black |
1
1.3%
|
| Caucasian |
67
88.2%
|
| Unknown |
7
9.2%
|
Outcome Measures
| Title | Clinical Benefit Rate (CBR) at 24 Weeks of PDR001+LAG525 by Tumor Type in Multiple Solid Tumors and Lymphoma |
|---|---|
| Description | CBR is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) and Stable Disease (SD). Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression. CBR (CR+PR+SD) is reported overall and by tumor type. |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) |
| Arm/Group Title | PDR001+LAG525 |
|---|---|
| Arm/Group Description | PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001. |
| Measure Participants | 75 |
| Overall |
25
32.9%
|
| Small cell lung cancer |
3
3.9%
|
| Gastric/esophageal adenocarcinoma |
2
2.6%
|
| Castration resistant prostate adenocarcinoma (CRPC) |
5
6.6%
|
| Soft tissue sarcoma |
4
5.3%
|
| Ovarian adenocarcinoma |
2
2.6%
|
| Advanced well-differentiated neuroendocrine tumors |
6
7.9%
|
| Diffuse large B cell lymphoma (DLBCL) |
3
3.9%
|
| Title | Overall Response Rate (ORR) |
|---|---|
| Description | ORR is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. ORR (CR+PR) is reported overall (including all tumor types). |
| Time Frame | From start of treatment until end of treatment, assessed up to 113 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) |
| Arm/Group Title | PDR001+LAG525 |
|---|---|
| Arm/Group Description | PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001. |
| Measure Participants | 75 |
| Count of Participants [Participants] |
7
9.2%
|
| Title | Time to Response (TTR) |
|---|---|
| Description | TTR is defined as the time from the date of first dose to the date of first documented response of Complete Response (CR) or Partial Response (PR). In case of solid tumor if a patient did not achieve a confirmed response they were censored at maximum follow-up for patients who had a PFS event (progressed or died due to any cause), or at last adequate tumor assessment date otherwise. Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007). |
| Time Frame | From start of treatment to the first documented response of either complete response or partial response, assessed up to 113 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) |
| Arm/Group Title | PDR001+LAG525 |
|---|---|
| Arm/Group Description | PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001. |
| Measure Participants | 75 |
| Median (95% Confidence Interval) [months] |
NA
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | DOR only applies to subjects for whom best overall response is complete response (CR) or partial response (PR). DOR is defined as the time between the date of first documented response (CR or PR) and the date of first documented progression/relapse or death due to any cause within 150 days of the last study drug dose date. If a patient not had an event, duration was censored at the date of last adequate tumor assessment. Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007). |
| Time Frame | From first documented response (CR or PR) to first documented progression or death, assessed up to 113 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Full Analysis Set (FAS) for whom best overall response is complete response (CR) or partial response (PR) |
| Arm/Group Title | PDR001+LAG525 |
|---|---|
| Arm/Group Description | PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001. |
| Measure Participants | 7 |
| Median (95% Confidence Interval) [months] |
NA
|
| Title | Time to Progression (TTP) |
|---|---|
| Description | TTP is the time from start of treatment to the date of event defined as the first documented progression or death due to underlying cancer. If a patient not had an event, time to progression was censored at the date of last adequate tumor assessment. Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007). |
| Time Frame | From start of treatment to first documented progression or death due to underlying cancer, assessed up to 113 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) |
| Arm/Group Title | PDR001+LAG525 |
|---|---|
| Arm/Group Description | PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001. |
| Measure Participants | 75 |
| Median (95% Confidence Interval) [months] |
2.8
|
| Title | Progression-Free Survival (PFS) |
|---|---|
| Description | PFS is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause within 150 days of the last dose. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Tumor response was based on local investigator assessment. For participants with solid tumors the assessment criteria was Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and for participants with lymphoma the assessment criteria was the Revised Response Criteria for Malignant Lymphoma (Cheson et al 2007). |
| Time Frame | From start of treatment to first documented progression or death, assessed up to 113 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full Analysis Set (FAS) |
| Arm/Group Title | PDR001+LAG525 |
|---|---|
| Arm/Group Description | PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001. |
| Measure Participants | 75 |
| Median (95% Confidence Interval) [months] |
2.8
|
| Title | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | Number of participants with AEs and SAEs including changes in laboratory parameters, vital signs and ECGs qualifying and reported as AEs. |
| Time Frame | From first dose of study treatment until last dose of study treatment plus 150 days post treatment, assessed up to 135 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study treatment |
| Arm/Group Title | PDR001+LAG525 |
|---|---|
| Arm/Group Description | PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001. |
| Measure Participants | 76 |
| AEs |
75
98.7%
|
| SAEs |
32
42.1%
|
| Title | Number of Participants With Dose Interruptions and Permanent Discontinuation of Study Drug |
|---|---|
| Description | Number of participants with at least one dose interruption of PDR001 and LAG525 and number of participants with permanent dose discontinuation of PDR001 and LAG525. |
| Time Frame | From first dose of study treatment until last dose of study treatment, assessed up to 113 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study treatment |
| Arm/Group Title | PDR001+LAG525 |
|---|---|
| Arm/Group Description | PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001. |
| Measure Participants | 76 |
| PDR001 - dose interruption |
30
39.5%
|
| PDR001 - permanent dose discontinuation |
72
94.7%
|
| LAG525 - dose interruption |
30
39.5%
|
| LAG525 - permanent dose discontinuation |
72
94.7%
|
| Title | Dose Intensity |
|---|---|
| Description | Dose intensity (mg/day) of PDR001 and LAG525 is calculated as cumulative dose in milligrams divided by duration of exposure in days. |
| Time Frame | From first dose of study treatment until last dose of study treatment, assessed up to 113 weeks. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study treatment |
| Arm/Group Title | PDR001+LAG525 |
|---|---|
| Arm/Group Description | PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001. |
| Measure Participants | 76 |
| PDR001 |
14.1
(0.88)
|
| LAG525 |
18.8
(1.20)
|
Adverse Events
| Time Frame | In the on-treatment period, adverse events (AEs) and serious AEs (including the All-Cause Mortality data table) are presented from first dose of study treatment until last dose of study treatment plus 30 days post treatment. In the extended safety follow-up period, AEs and serious AEs (including the All-Cause Mortality data table) are presented from day 31 to day 150 after last administration of study treatment. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | In the on-treatment period, any sign or symptom that occurs during the study treatment plus 30 days post treatment. In the extended safety follow-up period, any sign or symptom that occurs between 31 and 150 days post treatment. | |||
| Arm/Group Title | PDR001+LAG525 On-treatment Period | PDR001+LAG525 Extended Safety Follow-up Period | ||
| Arm/Group Description | PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001 | PDR001 300 mg and LAG525 400 mg administered via i.v. infusion over 30 minutes once every 3 weeks (Q3W). LAG525 was given first followed by PDR001 | ||
All Cause Mortality |
||||
| PDR001+LAG525 On-treatment Period | PDR001+LAG525 Extended Safety Follow-up Period | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 9/76 (11.8%) | 18/76 (23.7%) | ||
Serious Adverse Events |
||||
| PDR001+LAG525 On-treatment Period | PDR001+LAG525 Extended Safety Follow-up Period | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 31/76 (40.8%) | 4/76 (5.3%) | ||
| Blood and lymphatic system disorders | ||||
| Lymphadenopathy | 1/76 (1.3%) | 0/76 (0%) | ||
| Cardiac disorders | ||||
| Atrial fibrillation | 1/76 (1.3%) | 0/76 (0%) | ||
| Atrial flutter | 1/76 (1.3%) | 0/76 (0%) | ||
| Cardiac failure congestive | 1/76 (1.3%) | 0/76 (0%) | ||
| Pericardial effusion | 1/76 (1.3%) | 0/76 (0%) | ||
| Ventricular extrasystoles | 0/76 (0%) | 1/76 (1.3%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 2/76 (2.6%) | 0/76 (0%) | ||
| Abdominal pain lower | 1/76 (1.3%) | 0/76 (0%) | ||
| Haematemesis | 1/76 (1.3%) | 0/76 (0%) | ||
| Nausea | 2/76 (2.6%) | 0/76 (0%) | ||
| Vomiting | 2/76 (2.6%) | 0/76 (0%) | ||
| General disorders | ||||
| Asthenia | 3/76 (3.9%) | 0/76 (0%) | ||
| Infusion related reaction | 1/76 (1.3%) | 0/76 (0%) | ||
| Hepatobiliary disorders | ||||
| Autoimmune hepatitis | 1/76 (1.3%) | 0/76 (0%) | ||
| Infections and infestations | ||||
| Bacteraemia | 1/76 (1.3%) | 0/76 (0%) | ||
| Clostridium difficile infection | 1/76 (1.3%) | 0/76 (0%) | ||
| Enterocolitis infectious | 1/76 (1.3%) | 0/76 (0%) | ||
| Pneumonia | 5/76 (6.6%) | 0/76 (0%) | ||
| Pyelonephritis | 1/76 (1.3%) | 0/76 (0%) | ||
| Sepsis | 1/76 (1.3%) | 0/76 (0%) | ||
| Urinary tract infection | 1/76 (1.3%) | 0/76 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Fall | 1/76 (1.3%) | 0/76 (0%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 1/76 (1.3%) | 0/76 (0%) | ||
| Aspartate aminotransferase increased | 1/76 (1.3%) | 0/76 (0%) | ||
| Weight decreased | 1/76 (1.3%) | 0/76 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 1/76 (1.3%) | 0/76 (0%) | ||
| Dehydration | 1/76 (1.3%) | 0/76 (0%) | ||
| Hyponatraemia | 1/76 (1.3%) | 0/76 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 2/76 (2.6%) | 0/76 (0%) | ||
| Neck pain | 1/76 (1.3%) | 0/76 (0%) | ||
| Nervous system disorders | ||||
| Myelitis transverse | 1/76 (1.3%) | 1/76 (1.3%) | ||
| Spinal cord compression | 0/76 (0%) | 1/76 (1.3%) | ||
| Psychiatric disorders | ||||
| Failure to thrive | 1/76 (1.3%) | 0/76 (0%) | ||
| Mental status changes | 1/76 (1.3%) | 0/76 (0%) | ||
| Renal and urinary disorders | ||||
| Haematuria | 1/76 (1.3%) | 0/76 (0%) | ||
| Urinary retention | 1/76 (1.3%) | 0/76 (0%) | ||
| Acute kidney injury | 0/76 (0%) | 1/76 (1.3%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory failure | 2/76 (2.6%) | 0/76 (0%) | ||
| Pleural effusion | 1/76 (1.3%) | 0/76 (0%) | ||
| Pneumonitis | 2/76 (2.6%) | 0/76 (0%) | ||
| Vascular disorders | ||||
| Superior vena cava syndrome | 1/76 (1.3%) | 0/76 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| PDR001+LAG525 On-treatment Period | PDR001+LAG525 Extended Safety Follow-up Period | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 74/76 (97.4%) | 12/76 (15.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 13/76 (17.1%) | 2/76 (2.6%) | ||
| Cardiac disorders | ||||
| Dizziness | 6/76 (7.9%) | 2/76 (2.6%) | ||
| Dyspnoea | 18/76 (23.7%) | 1/76 (1.3%) | ||
| Oedema peripheral | 10/76 (13.2%) | 1/76 (1.3%) | ||
| Endocrine disorders | ||||
| Hypercalcaemia | 5/76 (6.6%) | 0/76 (0%) | ||
| Eye disorders | ||||
| Dry eye | 4/76 (5.3%) | 0/76 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal distension | 8/76 (10.5%) | 0/76 (0%) | ||
| Abdominal pain | 14/76 (18.4%) | 0/76 (0%) | ||
| Constipation | 20/76 (26.3%) | 0/76 (0%) | ||
| Diarrhoea | 15/76 (19.7%) | 1/76 (1.3%) | ||
| Dry mouth | 6/76 (7.9%) | 0/76 (0%) | ||
| Dysgeusia | 4/76 (5.3%) | 0/76 (0%) | ||
| Dyspepsia | 4/76 (5.3%) | 1/76 (1.3%) | ||
| Dysphagia | 4/76 (5.3%) | 0/76 (0%) | ||
| Flatulence | 5/76 (6.6%) | 0/76 (0%) | ||
| Gastrooesophageal reflux disease | 4/76 (5.3%) | 0/76 (0%) | ||
| Nausea | 26/76 (34.2%) | 1/76 (1.3%) | ||
| Vomiting | 20/76 (26.3%) | 0/76 (0%) | ||
| General disorders | ||||
| Chills | 6/76 (7.9%) | 0/76 (0%) | ||
| Fatigue | 28/76 (36.8%) | 0/76 (0%) | ||
| Non-cardiac chest pain | 4/76 (5.3%) | 0/76 (0%) | ||
| Pyrexia | 7/76 (9.2%) | 0/76 (0%) | ||
| Hepatobiliary disorders | ||||
| Ascites | 5/76 (6.6%) | 1/76 (1.3%) | ||
| Infections and infestations | ||||
| Urinary tract infection | 4/76 (5.3%) | 1/76 (1.3%) | ||
| Injury, poisoning and procedural complications | ||||
| Fall | 7/76 (9.2%) | 1/76 (1.3%) | ||
| Investigations | ||||
| Aspartate aminotransferase increased | 5/76 (6.6%) | 0/76 (0%) | ||
| Blood alkaline phosphatase increased | 5/76 (6.6%) | 0/76 (0%) | ||
| Blood creatinine increased | 10/76 (13.2%) | 0/76 (0%) | ||
| Weight decreased | 7/76 (9.2%) | 0/76 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 22/76 (28.9%) | 0/76 (0%) | ||
| Dehydration | 9/76 (11.8%) | 0/76 (0%) | ||
| Hypomagnesaemia | 6/76 (7.9%) | 0/76 (0%) | ||
| Hyponatraemia | 10/76 (13.2%) | 0/76 (0%) | ||
| Hypothyroidism | 6/76 (7.9%) | 1/76 (1.3%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 7/76 (9.2%) | 0/76 (0%) | ||
| Back pain | 13/76 (17.1%) | 1/76 (1.3%) | ||
| Muscular weakness | 7/76 (9.2%) | 0/76 (0%) | ||
| Musculoskeletal chest pain | 4/76 (5.3%) | 0/76 (0%) | ||
| Musculoskeletal pain | 8/76 (10.5%) | 0/76 (0%) | ||
| Myalgia | 4/76 (5.3%) | 0/76 (0%) | ||
| Pain in extremity | 4/76 (5.3%) | 0/76 (0%) | ||
| Nervous system disorders | ||||
| Headache | 11/76 (14.5%) | 0/76 (0%) | ||
| Insomnia | 8/76 (10.5%) | 1/76 (1.3%) | ||
| Psychiatric disorders | ||||
| Anxiety | 6/76 (7.9%) | 0/76 (0%) | ||
| Depression | 6/76 (7.9%) | 0/76 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 12/76 (15.8%) | 0/76 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Dry skin | 5/76 (6.6%) | 0/76 (0%) | ||
| Pruritus | 6/76 (7.9%) | 1/76 (1.3%) | ||
| Rash | 9/76 (11.8%) | 0/76 (0%) | ||
| Rash maculo-papular | 6/76 (7.9%) | 2/76 (2.6%) | ||
| Vascular disorders | ||||
| Hypertension | 4/76 (5.3%) | 0/76 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. Novartis does not prohibit any investigator from publishing. Any publications from a single site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
| Novartis.email@novartis.com |
- CPDR001XUS01