Lung Cancer, Non-Small Cell
Conditions
Keywords
GSK4069889A, GSK4057190A, Cobolimab, Dostarlimab, Docetaxel, Chemotherapy
Brief summary
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.
Interventions
BIOLOGICALCobolimab
Cobolimab will be administered.
BIOLOGICALDostarlimab
Dostarlimab will be administered.
DRUGDocetaxel
Docetaxel will be administered.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) (Arm A Versus Arm C) | Up to approximately 234 weeks | OS is defined as the time from the date of randomization to the date of death due to any cause. |
| Overall Survival (OS) (Arm B Versus Arm C) | Up to approximately 234 weeks | OS is defined as the time from the date of randomization to the date of death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Up to approximately 234 weeks | 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). |
| Progression Free Survival (PFS) | Up to approximately 234 weeks | 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.) |
| Duration of Response (DOR) | Up to approximately 234 weeks | 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). |
| 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 | 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) | 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. |
| 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 | 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) | 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. |
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | Baseline (Day-1) up to Cycle 1 Day 1 | 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). |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs (SAEs) and Immune-mediate AEs (imAEs) | Up to 329 weeks | 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). |
| Number of Participants With TEAEs Leading to Death and Treatment Discontinuation | Up to 329 weeks | 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. |
| Number of Participants Using Concomitant Medications | Up to 329 weeks | Number of participants using concomitant medications will be presented. |
| Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline | Up to 329 weeks | Blood samples will be collected for the analysis of hematology parameters. |
| Number of Participants With Worst Case Clinical Chemistry Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Up to 329 weeks | Blood samples will be collected for the analysis of Clinical Chemistry parameters. |
| Number of Participants With Worst Case Thyroid Function Results by Maximum Grade Increase Post-Baseline Relative to Baseline | Up to 329 weeks | Blood samples will be collected for the analysis of thyroid function |
| Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline | Up to 329 weeks | Urine samples will be collected to analyze urine specific gravity. |
| Number of Participants With Worst Case Vital Signs Results Relative to Normal Range Post-Baseline Relative to Baseline | Up to 329 weeks | Vital signs will be assessed |
| Number of Participants With Maximum Grade Increase Post-Baseline Relative to Baseline in Vital Signs | Baseline (Day -1) and Up to 281 weeks | Vital signs will be assessed and presented |
| Number of Participants With Indicated Eastern Cooperative Oncology Group (ECOG) Performance Status | Up to 329 weeks | Performance status will be assessed using the ECOG performance status scale. |
| Time to Deterioration (TTD) in Lung Cancer | Up to approximately 234 weeks | 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). |
| Number of Participants With Abnormal Physical Examinations | Up to approximately 234 weeks | Number of participants with abnormal physical examinations will be presented |
| Overall Survival (OS) (Arm A Versus Arm B) | Up to approximately 234 weeks | OS is defined as the time from the date of randomization to the date of death due to any cause. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Finland, France, Germany, Greece, Italy, Japan, Mexico, Netherlands, Poland, Romania, Russia, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Participant flow
Pre-assignment details
The results presented are based on primary completion date. Safety data collection (except ECG findings) is still ongoing, and additional results will be provided within a year of study completion.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 64.0 YEARS STANDARD_DEVIATION 9.37 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 5 Participants |
| Race/Ethnicity, Customized Asian | 44 Participants |
| Race/Ethnicity, Customized Black or African American | 11 Participants |
| Race/Ethnicity, Customized Mixed Race | 1 Participants |
| Race/Ethnicity, Customized Not Reported | 2 Participants |
| Race/Ethnicity, Customized Unknown | 2 Participants |
| Race/Ethnicity, Customized White | 588 Participants |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 207 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 227 / 305 | 236 / 301 | 116 / 152 |
| other Total, other adverse events | 285 / 302 | 276 / 295 | 136 / 144 |
| serious Total, serious adverse events | 102 / 302 | 126 / 295 | 52 / 144 |
Outcome results
None listed