Efficacy Comparison of Dostarlimab Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy in Participants With Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC)

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04581824
Collaborator
(none)
244
66
2
59
3.7
0.1

Study Details

Study Description

Brief Summary

NSCLC comprises of approximately 84 percent (%) of all lung cancers and is often diagnosed at advanced stage due to poor prognosis. Dostarlimab is an immunoglobulin G (IgG)4 kappa humanized monoclonal antibody (mAb) that binds with high affinity to programmed cell death protein 1 (PD 1), resulting in inhibition of binding to programmed death ligand 1 (PD L1) and programmed death ligand 2 (PD L2). This study aims to compare the efficacy and safety PD-1 inhibitors dostarlimab and pembrolizumab, when administered in combination with chemotherapy (pemetrexed, cisplatin and carboplatin), in participants with non-squamous NSCLC without a known sensitizing epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or receptor tyrosine kinase-1 (ROS-1) mutation, BRAF V600E mutation, or other genomic aberration for which an approved targeted therapy is available. A total of approximately 240 participants will be enrolled in the study for a period of 5 years.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
244 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Care Provider)
Masking Description:
Participants and study staff may only be blinded to study treatment.
Primary Purpose:
Treatment
Official Title:
A Randomized, Phase 2, Double-blind Study to Evaluate the Efficacy of Dostarlimab Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy in Metastatic Non-Squamous Non-Small Cell Lung Cancer
Actual Study Start Date :
Nov 19, 2020
Anticipated Primary Completion Date :
Aug 4, 2022
Anticipated Study Completion Date :
Oct 20, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Participants receiving dostarlimab plus chemotherapy

Participants will receive dostarlimab on Day 1 of every 21 Day cycle followed by pemetrexed, and then followed by cisplatin or carboplatin (Cycles 1 to 4 only) as per investigator decision.

Drug: Dostarlimab
Dostarlimab will be administered through a 30 minute infusion at a dose of 500 milligrams (mg) intravenously (IV) every 3 weeks (Q3W) up to a maximum of 35 cycles (each cycle of 21 days).

Drug: Chemotherapy
Pemetrexed will be administered at 500 milligram per meter square (mg/m^2 ) IV through a 10 minute IV infusion Q3W, up to a maximum of 35 cycles (each cycle of 21 days). Cisplatin will be administered at 75 mg/m^2 through a 30 minute IV infusion Q3W for 4 cycles (each cycle of 21 days) as per investigator decision. Carboplatin will also be administered at area under the concentration time curve 5 milligram/milliliters/minute (mg/mL/min) (maximum dose: 750 mg) through a 15 to 60 minute IV infusion Q3W for 4 cycles (each cycle of 21 days) as per investigator decision.

Active Comparator: Participants receiving pembrolizumab plus chemotherapy

Participants will receive pembrolizumab on Day 1 of every 21 Day cycle followed by pemetrexed, and then followed by cisplatin or carboplatin (Cycles 1 to 4 only) as per investigator decision.

Drug: Pembrolizumab
Pembrolizumab will be administered through a 30 minute infusion at a dose of 200 mg Q3W up to a maximum of 35 cycles (each cycle of 21 days).

Drug: Chemotherapy
Pemetrexed will be administered at 500 milligram per meter square (mg/m^2 ) IV through a 10 minute IV infusion Q3W, up to a maximum of 35 cycles (each cycle of 21 days). Cisplatin will be administered at 75 mg/m^2 through a 30 minute IV infusion Q3W for 4 cycles (each cycle of 21 days) as per investigator decision. Carboplatin will also be administered at area under the concentration time curve 5 milligram/milliliters/minute (mg/mL/min) (maximum dose: 750 mg) through a 15 to 60 minute IV infusion Q3W for 4 cycles (each cycle of 21 days) as per investigator decision.

Outcome Measures

Primary Outcome Measures

  1. Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). [Up to 5 years]

    ORR will be evaluated by RECIST v1.1 based on blinded independent central review (BICR) and will be defined as the proportion of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) in the analysis population.

Secondary Outcome Measures

  1. Overall survival (OS) [Up to 5 years]

    OS is defined as the time from the date of randomization to the date of death by any cause.

  2. Progression free survival (PFS) by RECIST v1.1 [Up to 5 years]

    PFS will be evaluated using RECIST v1.1 based on Investigator assessment and is defined as the time from the date of randomization to the date of progressive disease (PD) or death by any cause, whichever occurs first.

  3. Number of participants with treatment-emergent adverse events (TEAEs) [Up to 5 years]

    A TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment.

  4. Number of participants with serious adverse events (SAEs) [Up to 5 years]

    An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect or is an important medical event that may jeopardize the participant or may require medical or surgical intervention to prevent one of the above outcomes

  5. Number of participants with immune related adverse events (irAEs) [Up to 5 years]

    The irAEs are events which may be severe or fatal and can occur in participants treated with monoclonal antibodies directed against immune checkpoints, including pembrolizumab and dostarlimab. While irAEs (eg, diarrhea/colitis, pneumonitis, nephritis, hypophysitis, adrenalitis, thyroiditis, severe skin reactions, uveitis, myocarditis, and hepatotoxicity) usually occur during treatment, symptoms can also manifest after discontinuation of treatment.

  6. Number of participants with TEAEs leading to death [Up to 5 years]

    Number of participants with TEAEs leading to death will be assessed.

  7. Number of participants with adverse events leading to discontinuation (AELD) [Up to 5 years]

    Number of participants with AELDs will be assessed.

  8. Number of participants with clinically significant changes in hematology, clinical chemistry, thyroid function and urinalysis lab parameters. [Up to 5 years]

    Blood and urine samples will be collected to evaluate hematology, clinical chemistry, thyroid function and urinalysis lab parameters.

  9. Number of participants with abnormal vital signs [Up to 5 years]

    Number of participants with abnormal vital signs will be assessed.

  10. Number of participants with abnormal Eastern Cooperative Oncology Group (ECOG) performance status [Up to 5 years]

    Performance status will be assessed using the ECOG scale (Grade 0-4). Grade 0 indicates fully active, able to carry on all pre-disease performance without restriction and Grade 4 indicates completely disabled, cannot carry on any self-care and totally confined to bed or chair.

  11. Number of participants with abnormal electrocardiogram (ECG) parameters [Up to 5 years]

    Participants will be supine or in a semi-recumbent position and rested for approximately 2 minutes before ECGs are recorded.

  12. Number of participants with abnormal physical examination [Up to 5 years]

    Physical examination will include assessments of the cardiovascular, respiratory, gastrointestinal, and neurological systems. Height and weight will also be measured and recorded.

  13. Number of participants receiving concomitant medications [Up to 5 years]

    Concomitant medications will be recorded.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Participant must be greater than equal to (>=) 18 years old, must be able to understand the study procedures, and agrees to participate in the study by providing written informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

  • Participant has histologically- or cytologically-confirmed metastatic non-squamous NSCLC with documented absence of a sensitizing EGFR, ALK, ROS-1, or BRAFV600E mutation or other genomic aberration for which an approved targeted therapy is available. Mixed tumors will be categorized by the predominant cell type; if the tumor has predominantly squamous cell histology or if small cell elements are present, the participant is ineligible.

  • Participants must have measurable disease, that is (i.e.) presenting with at least 1 measurable lesion per RECIST v1.1 as determined by the local site Investigator/radiology assessment. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions and if there are other target lesions. If there is only 1 target lesion that was previously irradiated, the participant is not eligible.

  • Participant has documented PD L1 status by the 22C3 pharmDx assay (Agilent/Dako). If no prior PD L1 result is available at the time of Screening, the participant can be tested locally using the stated method, or central PD L1 testing can be completed. Results are needed for stratification and must be available prior to randomization.

  • Participant has an ECOG performance status score of 0 or 1.

  • Participant has a life expectancy of at least 3 months.

  • Participant has adequate organ function.

  • Participant has recovered to Grade less than equal to (<=)1 from any prior treatment related toxicities at the time of randomization. A participant with Grade 2 alopecia is an exception to this criterion and may qualify for this study.

  • Contraceptive use by male and female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

  • Male participants are eligible to participate if they agree to the following during the Treatment Period and for at least 150 days after the last dose of study treatment:

  • Refrain from donating sperm plus, either:

  • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent.

  • Must agree to use contraception/barrier as follows:

  • Agree to use a male condom (and should also be advised of the benefit for a female partner to use a highly effective method of contraception, as a condom may break or leak) when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant.

  • Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person.

  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies:

  • Is a woman of non childbearing potential (WONCBP),

  • Is a WOCBP, using a contraceptive method that is highly effective (with a failure rate of <1% per year and, preferably, with low user dependency) during the Treatment Period and for at least 180 days after the last dose of study treatment and agrees not to donate eggs (ova or oocytes) for the purpose of reproduction during this period. The Investigator should evaluate the potential for contraceptive method failure ( for example [e.g.], noncompliance and recently initiated) in relationship to the first dose of study treatment.

  • A WOCBP must have a negative highly sensitive pregnancy test (urine or serum, as required by local guidelines) within 72 hours before the first dose of study treatment. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.

Exclusion Criteria:
  • Participant has received prior systemic therapy for the treatment of metastatic NSCLC. Participants who have received neoadjuvant or adjuvant chemotherapy are eligible if the neoadjuvant/adjuvant therapy was completed at least 12 months prior to the development of metastatic disease.

  • Participant has received prior therapy with a PD (L)1 or PD L2 inhibitor, a cytotoxic T lymphocyte associated protein 4 (CTLA 4) inhibitor, a T cell immunoglobulin and mucin domain containing 3 (TIM 3) inhibitor, or any other immunotherapy agent (eg, OX40) for the treatment of cancer.

  • Participant has received radiation to the lung that is >30 Gray (Gy) within 6 months of the first dose of study treatment.

  • Participant has completed palliative radiotherapy within 7 days of the first dose of study treatment.

  • Participant is ineligible if any of the following hepatic characteristics are present:

  • Alanine aminotransferase (ALT) >2.5 times upper limit of normal (ULN) without liver metastases/tumor infiltration.

  • ALT >5 times ULN with liver metastases/tumor infiltration.

  • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%)

  • Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease per Investigator assessment)

  • Participant has a corrected QT interval (QTc) >450 milliseconds (msec) (or QTc >480 msec for participants with bundle branch block).

  • Participant has had major surgery within 3 weeks of the first dose of study treatment or has not adequately recovered from any AEs (Grade <=1) and/or complications from any major surgery. Surgical implantation of a port catheter is not exclusionary.

  • Participant has an additional malignancy or a history of prior malignancy, with the exception of adequately treated basal or squamous skin cancer, cervical carcinoma in situ, or bladder carcinoma in situ without evidence of disease, or had a malignancy treated with curative intent and with no evidence of disease recurrence for 5 years since the initiation of that therapy.

  • Participant has known active brain metastases and/or leptomeningeal metastases. Participants who have received prior therapy for their brain metastases and have radiographically stable central nervous system disease may participate, provided they are neurologically stable for at least 2 weeks before study entry and must be off corticosteroids within 3 days prior to the first dose of study treatment. Stable brain metastases by this definition should be established prior to the first dose of study treatment. Participants with known untreated, asymptomatic brain metastases (i.e., no neurological symptoms, no requirements for corticosteroids, no or minimal surrounding edema, and no lesions >1.5 centimeters [cm]) may participate, but will require regular imaging of the brain as a site of disease.

  • Participant has tested positive for the presence of hepatitis B surface antigen or has a positive hepatitis C antibody test result at Screening, or within 3 months prior to first dose of study treatment. For potent immunosuppressive agents, participants who test positive for the presence of hepatitis B core antibody should also be excluded.

  • Participant has an active infection requiring systemic therapy within 1 week prior to the anticipated first dose of study treatment.

  • Participant has known human immunodeficiency virus (HIV) (positive for HIV 1 or HIV 2 antibodies).

  • Participant has active autoimmune disease that required systemic treatment in the past 2 years, is immunocompromised in the opinion of the Investigator, or is receiving systemic immunosuppressive treatment. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.

  • Participant has received systemic steroid therapy within 3 days prior to the first dose of the study treatment or is receiving any other form of immunosuppressive medication. Replacement therapy is not considered a form of systemic therapy. Use of inhaled corticosteroids, local steroid injection, or steroid eye drops is allowed.

  • Participant has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment of these conditions (including therapeutic thoraco or paracentesis) is eligible.

  • Participant has current interstitial lung disease, current pneumonitis, or a history of pneumonitis that required the use of oral or IV glucocorticoids to assist with management. Lymphangitic spread of the NSCLC is not exclusionary.

  • Participant has a history or current evidence of any medical condition, therapy, or laboratory abnormality that might confound the study results, interfere with their participation for the full duration of the study treatment, or indicate it is not in the best interest of the participant to participate, in the opinion of the Investigator.

  • Participant has clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction, or peritoneal carcinomatosis.

  • Participant has preexisting peripheral neuropathy that is Grade >=2 by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 criteria.

  • Participant has received a live vaccine within 30 days of the first dose of study treatment. Seasonal flu vaccines that do not contain live virus are permitted.

  • Participant does not meet requirements per local prescribing guidelines for receiving treatment with either pemetrexed and cisplatin or carboplatin.

  • Participant has sensitivity to any of the study treatments, or components thereof, or a history of drug or other allergy that, in the opinion of the Investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation.

  • Participant is unable to interrupt aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs), other than an aspirin dose <=1.3 gram (g) per day, for a 5 day period (8 day period for long acting agents, such as piroxicam).

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Lone Tree Colorado United States 80128
2 GSK Investigational Site Palm Bay Florida United States 32909
3 GSK Investigational Site Pensacola Florida United States 32503
4 GSK Investigational Site Cincinnati Ohio United States 45242
5 GSK Investigational Site Dallas Texas United States 75237
6 GSK Investigational Site Tyler Texas United States 75702
7 GSK Investigational Site Fairfax Virginia United States 22031
8 GSK Investigational Site Ciudad Autonoma de Buenos Aires Buenos Aires Argentina C1012AAR
9 GSK Investigational Site Ciudad Autónoma de Buenos Aires Buenos Aires Argentina C1426ABP
10 GSK Investigational Site Florida Buenos Aires Argentina 1602
11 GSK Investigational Site La Plata Buenos Aires Argentina 1900
12 GSK Investigational Site Pergamino Buenos Aires Argentina B2700CPM
13 GSK Investigational Site Viedma Río Negro Argentina R8500ACE
14 GSK Investigational Site Rosario Santa Fe Argentina S2000KZE
15 GSK Investigational Site Cordoba Argentina X5004FHP
16 GSK Investigational Site La Rioja Argentina F5300COE
17 GSK Investigational Site San Juan Argentina J5402DIL
18 GSK Investigational Site Fortaleza Ceará Brazil 60336-232
19 GSK Investigational Site Vitória Espírito Santo Brazil 29043-260
20 GSK Investigational Site Natal Rio Grande Do Norte Brazil 59075-740
21 GSK Investigational Site Lajeado Rio Grande Do Sul Brazil 95900-010
22 GSK Investigational Site Barretos São Paulo Brazil 14784-400
23 GSK Investigational Site Rio de Janeiro Brazil 20230 -130
24 GSK Investigational Site São Paulo Brazil 04014-002
25 GSK Investigational Site Providencia Región Metro De Santiago Chile 7500653
26 GSK Investigational Site Santiago Región Metro De Santiago Chile 8320000
27 GSK Investigational Site Caen Cedex 9 France 14033
28 GSK Investigational Site Le Mans France 72000
29 GSK Investigational Site Limoges Cedex France 87042
30 GSK Investigational Site Pessac cedex France 33604
31 GSK Investigational Site Saint Herblain cedex France 44805
32 GSK Investigational Site Valenciennes France 59300
33 GSK Investigational Site Aschaffenburg Bayern Germany 63739
34 GSK Investigational Site Frankfurt Hessen Germany 60488
35 GSK Investigational Site Immenhausen Hessen Germany 34376
36 GSK Investigational Site Oldenburg Niedersachsen Germany 26121
37 GSK Investigational Site Koeln Nordrhein-Westfalen Germany 51109
38 GSK Investigational Site Berlin Germany 12200
39 GSK Investigational Site Napoli Campania Italy 80131
40 GSK Investigational Site Aviano Friuli-Venezia-Giulia Italy 33081
41 GSK Investigational Site Roma Lazio Italy 00152
42 GSK Investigational Site Brescia Lombardia Italy 25123
43 GSK Investigational Site Milano Lombardia Italy 20133
44 GSK Investigational Site Milano Lombardia Italy 20141
45 GSK Investigational Site Catania Sicilia Italy 95125
46 GSK Investigational Site Busan Korea, Republic of 48108
47 GSK Investigational Site Cheongju-si, Chungcheongbuk-do Korea, Republic of 28644
48 GSK Investigational Site Seoul Korea, Republic of 05505
49 GSK Investigational Site Seoul Korea, Republic of 06351
50 GSK Investigational Site Seoul Korea, Republic of 120-752
51 GSK Investigational Site Bydgoszcz Poland 85-796
52 GSK Investigational Site Lodz Poland 90-242
53 GSK Investigational Site Lublin Poland 20-954
54 GSK Investigational Site Olsztyn Poland 10-357
55 GSK Investigational Site Pila Poland 64-920
56 GSK Investigational Site Poznan Poland 60-693
57 GSK Investigational Site Bucuresti Romania 030442
58 GSK Investigational Site Craiova Romania 200347
59 GSK Investigational Site Floresti Romania 407280
60 GSK Investigational Site Barcelona Spain 08003
61 GSK Investigational Site Jaén Spain 23007
62 GSK Investigational Site Lugo Spain 27003
63 GSK Investigational Site Málaga Spain 29010
64 GSK Investigational Site Sevilla Spain 41014
65 GSK Investigational Site Changhua Taiwan 500
66 GSK Investigational Site Taipei Taiwan 11490

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT04581824
Other Study ID Numbers:
  • 213403
First Posted:
Oct 9, 2020
Last Update Posted:
Jun 28, 2022
Last Verified:
Jun 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 GlaxoSmithKline
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 28, 2022