Clinical Trials /

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

NCT04581824

Description:

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.

Related Conditions:
  • Non-Squamous Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 213403
  • NCT ID: NCT04581824

Conditions

  • Lung Cancer, Non-Small Cell

Interventions

DrugSynonymsArms
DostarlimabParticipants receiving dostarlimab plus chemotherapy
PembrolizumabParticipants receiving pembrolizumab plus chemotherapy
ChemotherapyParticipants receiving dostarlimab plus chemotherapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Participants receiving dostarlimab plus chemotherapyExperimentalParticipants 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.
  • Dostarlimab
  • Chemotherapy
Participants receiving pembrolizumab plus chemotherapyActive ComparatorParticipants 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.
  • Pembrolizumab
  • Chemotherapy

Eligibility Criteria

        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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1).
Time Frame:Up to 5 years
Safety Issue:
Description: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

Measure:Overall survival (OS)
Time Frame:Up to 5 years
Safety Issue:
Description:OS is defined as the time from the date of randomization to the date of death by any cause.
Measure:Progression free survival (PFS) by RECIST v1.1
Time Frame:Up to 5 years
Safety Issue:
Description: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.
Measure:Number of participants with treatment-emergent adverse events (TEAEs)
Time Frame:Up to 5 years
Safety Issue:
Description: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.
Measure:Number of participants with serious adverse events (SAEs)
Time Frame:Up to 5 years
Safety Issue:
Description: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
Measure:Number of participants with immune related adverse events (irAEs)
Time Frame:Up to 5 years
Safety Issue:
Description: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.
Measure:Number of participants with TEAEs leading to death
Time Frame:Up to 5 years
Safety Issue:
Description:Number of participants with TEAEs leading to death will be assessed.
Measure:Number of participants with adverse events leading to discontinuation (AELD)
Time Frame:Up to 5 years
Safety Issue:
Description:Number of participants with AELDs will be assessed.
Measure:Number of participants with clinically significant changes in hematology, clinical chemistry, thyroid function and urinalysis lab parameters.
Time Frame:Up to 5 years
Safety Issue:
Description:Blood and urine samples will be collected to evaluate hematology, clinical chemistry, thyroid function and urinalysis lab parameters.
Measure:Number of participants with abnormal vital signs
Time Frame:Up to 5 years
Safety Issue:
Description:Number of participants with abnormal vital signs will be assessed.
Measure:Number of participants with abnormal Eastern Cooperative Oncology Group (ECOG) performance status
Time Frame:Up to 5 years
Safety Issue:
Description: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.
Measure:Number of participants with abnormal electrocardiogram (ECG) parameters
Time Frame:Up to 5 years
Safety Issue:
Description:Participants will be supine or in a semi-recumbent position and rested for approximately 2 minutes before ECGs are recorded.
Measure:Number of participants with abnormal physical examination
Time Frame:Up to 5 years
Safety Issue:
Description:Physical examination will include assessments of the cardiovascular, respiratory, gastrointestinal, and neurological systems. Height and weight will also be measured and recorded.
Measure:Number of participants receiving concomitant medications
Time Frame:Up to 5 years
Safety Issue:
Description:Concomitant medications will be recorded.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:GlaxoSmithKline

Trial Keywords

  • Non small cell lung cancer
  • Dostarlimab
  • Pembrolizumab
  • Pemetrexed
  • Carboplatin
  • Cisplatin

Last Updated

April 19, 2021