Efficacy Comparison of Cobolimab + Dostarlimab + Docetaxel to Dostarlimab + Docetaxel to Docetaxel Alone in Participants With Advanced Non-small Cell Lung Cancer Who Have Progressed on Prior Anti-PD-(L)1 Therapy and Chemotherapy

Phase 3Active Not RecruitingNCT04655976

GlaxoSmithKline758 enrolled

Overview

This is a multi-center, parallel group treatment, Phase 2/3 open label study evaluating cobolimab in combination with dostarlimab and docetaxel in participants with advanced non-small cell Lung Cancer (NSCLC) who have progressed on prior anti-PD-(L)1 therapy and chemotherapy.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

758

Conditions

Lung Cancer, Non-Small Cell

Interventions

CobolimabBIOLOGICAL

Cobolimab will be administered.

DostarlimabBIOLOGICAL

Dostarlimab will be administered.

DocetaxelDRUG

Docetaxel will be administered.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participant has histologically or cytologically proven advanced or metastatic NSCLC and only squamous or non-squamous cell carcinoma. * Participant has received no more than 2 prior lines of therapy for advanced or metastatic disease, which must only include a platinum based (e.g., cisplatin, carboplatin) doublet chemotherapy regimen and an anti-PD-1 or an anti-PD-(L)1 antibody. * Participant has measurable disease. * Participant has documented radiographic disease progression on prior platinum based chemotherapy and on or after prior anti-PD-(L)1 therapy. * Participant agrees to submit an archival formalin-fixed paraffin-embedded (FFPE) tumor tissue specimen that was collected on or after diagnosis of metastatic disease. If archival tissue is not available, the participant must undergo biopsy prior to study entry. * Participant has an ECOG performance status score of 0 or 1. * Participant has a life expectancy of at least 3 months. * Participant has adequate Baseline organ function. * Participant has recovered from any prior treatment related toxicities. * Participant agrees to use contraception. Exclusion Criteria: * Participant has been previously treated with an anti-PD-\[L\]1 or anti-programmed death-ligand 2 (anti-PD-\[L\]2) agent that resulted in permanent discontinuation due to an AE. * Participant has been previously treated with an anti-T cell immunoglobulin and mucin domain containing 3 (anti-TIM-3) or anti-cytotoxic T lymphocyte associated protein 4 (CTLA 4) agent or docetaxel. * Participant has a documented sensitizing epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or c-ros oncogene 1 (ROS-1) mutation. Participants whose tumors have not been tested for these driver mutations and therefore who have unknown driver mutation status are not eligible. Participants with squamous histology do not need to be tested for these driver mutations. * Participant had radiological or clinical disease progression (i.e., worsening performance status, clinical symptoms, and laboratory data) \<=8 weeks after initiation of prior anti-programmed cell death protein 1 (anti-PD-1) or anti-PD-L1 antibody. The clinical disease progression should have been confirmed by a subsequent radiological scan. * Participant has received radiation to the lung that is \>30 gray (Gy) within 6 months prior to the first dose of study treatment. * Participant has completed palliative radiotherapy within 7 days prior to the first dose of study treatment. * Participant is ineligible if any of the following hepatic characteristics are present: a. Alanine aminotransferase (ALT) \>2.5 times upper limit normal (ULN) b. ALT and/or aspartate aminotransferase (AST) \>1.5 times ULN concomitant with alkaline phosphatase (ALP) \>2.5 times ULN; c. Bilirubin \>1 times ULN; d. 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 the Investigator's assessment). * Participant has known new or progressive 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 4 weeks before study entry and are off corticosteroids within 3 days prior to the first dose of study treatment. * Participant has tested positive for the following at Screening or within 3 months before the first dose of study treatment: a. Presence of hepatitis B surface antigen. b. Presence of hepatitis C antibody in the absence of a ribonucleic acid (RNA) test for hepatitis C virus. If a confirmatory RNA test is available, a positive test result will exclude a participant, while a negative test result (indicating absence of active infection) will allow the participant to enter into the study. * 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. * Participant has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment of these conditions (including therapeutic thoracentesis or paracentesis) is eligible. * Participant has current interstitial lung disease, current pneumonitis, or a history of pneumonitis that required the use of glucocorticoids to assist with management. * Participant has pre-existing peripheral neuropathy that is Grade \>=2 by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 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 and Coronavirus Disease 2019 (COVID-19) vaccines. * Participant is unable to interrupt aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) for undergoing a biopsy procedure (in cases when a participant does not have an archival biopsy), other than an aspirin dose \<=1.3 grams (g) per day, for a 5-day period (8-day) period for long-acting agents, such as piroxicam).

Locations (163)

Outcomes

Primary Outcomes

Overall Survival (OS) (Arm A Versus Arm C)

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

Time frame: Up to approximately 234 weeks

Overall Survival (OS) (Arm B Versus Arm C)

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

Time frame: Up to approximately 234 weeks

Secondary Outcomes

Overall Survival (OS) (Arm A Versus Arm B)

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

Time frame: Up to approximately 234 weeks

Overall Response Rate (ORR)

ORR is defined as the percentage of participants who have achieved confirmed complete response (CR) or confirmed partial response (PR) as the best overall response based on Investigator assessment, evaluated using Response Evaluation Criteria in Solid Tumors Criteria (RECIST) version 1.1 . PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm).

Time frame: Up to approximately 234 weeks

Progression Free Survival (PFS)

PFS is defined as the length of time from randomization to the earliest date of assessment of disease progression based on RECIST v1.1 by Investigator assessment or death by any cause, whichever occurs first. Progressive Disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start. In addition, the sum has an absolute increase from nadir of 5 mm.)

Data from ClinicalTrials.gov

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GSK Investigational Site

Fountain Valley, California, United States

GSK Investigational Site

Walnut Creek, California, United States

GSK Investigational Site

Norwich, Connecticut, United States

GSK Investigational Site

Washington D.C., District of Columbia, United States

GSK Investigational Site

Honolulu, Hawaii, United States

GSK Investigational Site

Iowa City, Iowa, United States

GSK Investigational Site

Edgewood, Kentucky, United States

GSK Investigational Site

Las Vegas, Nevada, United States

GSK Investigational Site

Mineola, New York, United States

GSK Investigational Site

New York, New York, United States

...and 153 more locations

Time frame: Up to approximately 234 weeks

Duration of Response (DOR)

DOR is defined as the time from first documented response (CR/PR) until the time of first documentation of disease progression based on RECIST version 1.1 by Investigator assessment or death, whichever occurs first. PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). Progressive Disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start).

Time frame: Up to approximately 234 weeks

Time to Deterioration (TTD) in Lung Cancer

TTD in lung cancer is defined as time from randomization to meaningful deterioration on a composite endpoint of dyspnea, chest pain, and cough, from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 13 item Lung Cancer Module (EORTC-QLQ-LC13).

Time frame: Up to approximately 234 weeks

Change From Baseline (CFB) in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30) Score

The EORTC QLQ-C30 includes 30-items with single and multi-item scales. These include five functional scales (physical functioning \[PF\], role functioning \[RF\], emotional functioning \[EF\] cognitive functioning \[CF\] and social functioning \[SF\]), three symptom scales (fatigue, nausea/vomiting \[N/V\] and pain), a global health status (GHS)/ Quality-of-Life (QoL) scale, and six single items (dyspnea, insomnia, appetite loss \[AL\], constipation, diarrhea and financial difficulties \[FD\]). Response options are 1 (Not at all) to 4 (Very much). Scores were averaged and transformed to 0 to 100, a high score for functional scales/ GHS/QoL represent better functioning ability or health-related quality-of-life (HRQoL), whereas a high score for symptom scales/ single items represent significant symptomatology. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Time frame: Baseline [Day(D) -1],D1 on Cycle(C)(s) 2,3,4,5,6,9,12,15,18,22,26,30,34,38,42,46,50,54, 58,62,66, End of treatment (EoT- up to approximately(~) 216 weeks), Safety follow up (SFU) at D30 after EOT (~ 220 weeks) & at D90 after EOT (~ 229 weeks)

Change From Baseline in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 13 Item Lung Cancer Module (EORTC-QLQ-LC13) Assessment

The QLQ-LC13 questionnaire comprises 13 questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea and site-specific pain which includes pain in chest, pain in arm or shoulder and pain in other parts), and treatment-related side effects (sore mouth \[SM\], dysphagia, peripheral neuropathy \[PN\] and alopecia). Response options are 1 (Not at all) to 4 (Very much). Scores were averaged and transformed to 0 to 100. Higher scores represent increasing symptom levels. Baseline is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Time frame: Baseline (D -1),D1 on Cycle(C)(s) 2,3,4,5,6,9,12,15,18,22,26,30,34,38,42,46,50,54, 58,62,66, End of treatment (EoT- up to approximately(~) 216 weeks), Safety follow up (SFU) at D30 after EOT (~ 220 weeks) & at D90 after EOT (~ 229 weeks)

Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings

ECGs were recorded after the participants were in a supine or semi-recumbent position (about 30 degrees of elevation) and rested for approximately 2 minutes. ECG findings are summarized as clinically significant change from baseline worst case hierarchy: Yes \> No \> Not Applicable (NA).

Time frame: Baseline (Day-1) up to Cycle 1 Day 1

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs (SAEs) and Immune-mediate AEs (imAEs)

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. SAE is defined as any untoward medical occurrence that, at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs. AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA dictionary).

Time frame: Up to 329 weeks

Number of Participants With TEAEs Leading to Death and Treatment Discontinuation

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.

Time frame: Up to 329 weeks

Number of Participants Using Concomitant Medications

Number of participants using concomitant medications will be presented.

Time frame: Up to 329 weeks

Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples will be collected for the analysis of hematology parameters.

Time frame: Up to 329 weeks

Number of Participants With Worst Case Clinical Chemistry Results by Maximum Grade Increase Post-Baseline Relative to Baseline

Blood samples will be collected for the analysis of Clinical Chemistry parameters.

Time frame: Up to 329 weeks

Number of Participants With Worst Case Thyroid Function Results by Maximum Grade Increase Post-Baseline Relative to Baseline

Blood samples will be collected for the analysis of thyroid function

Time frame: Up to 329 weeks

Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline

Urine samples will be collected to analyze urine specific gravity.

Time frame: Up to 329 weeks

Number of Participants With Worst Case Vital Signs Results Relative to Normal Range Post-Baseline Relative to Baseline

Vital signs will be assessed

Time frame: Up to 329 weeks

Number of Participants With Maximum Grade Increase Post-Baseline Relative to Baseline in Vital Signs

Vital signs will be assessed and presented

Time frame: Baseline (Day -1) and Up to 281 weeks

Number of Participants With Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status

Performance status will be assessed using the ECOG performance status scale.

Time frame: Up to 329 weeks

Number of Participants With Abnormal Physical Examinations

Number of participants with abnormal physical examinations will be presented

Time frame: Up to approximately 234 weeks