Nonsmall Cell Lung Cancer (NSCLC) MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: 1. Participant is =18 years old, is able to understand the study procedures, and agrees to participate in the study by providing written informed consent (as described in APPENDIX 5), which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Note: Participants in Korea are eligible if they are 19 years or older at the time consent is obtained. 2. Participant has histologically or cytologically proven advanced or metastatic NSCLC, and only squamous or nonsquamous cell carcinoma. 3. 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 anti-PD-L1 antibody (no other biologic alone or in combination; novel combinations are not allowed). Participants previously treated with targeted therapies, including angiogenesis inhibitors (e.g., bevacizumab, ramucirumab, lenvatinib), are not eligible. Two components of treatment must have been received in the same line or as separate lines of therapy as follows: • A maximum of 1 line of therapy containing a platinum-based chemotherapy in the metastatic setting and • A maximum of 1 line of therapy containing an anti-PD-1 or anti-PD-L1 antibody Note the following: - An anti-PD-1 or anti-PD-L1 antibody received during a previous clinical study meets this requirement if the antibody has been approved for an indication in at least 1 country. - Participants from the Phase 3 PACIFIC clinical study (NCT02125461) who received the experimental regimen (chemoradiotherapy followed by durvalumab) (Antonia, 2017) or participants who received a regimen similar to the PACIFIC regimen (chemoradiotherapy followed by an antiPD-1 or anti-PD-L1 antibody) as part of standard of care and have relapsed within 1 year of the first dose of chemoradiotherapy fulfill the protocol requirement for platinum-based chemotherapy and anti-PD-1 or anti-PD-L1 antibody therapy. These regimens are considered 1 line of therapy for stratification purposes. - The anti-PD-1 or anti-PD-L1 antibody can be administered with the platinum-based chemotherapy, and this is considered 1 line of therapy with both agents and no other lines are allowed. - The anti-PD-1 or anti-PD-L1 antibody may be counted as a prior treatment if the antibody is approved in at least 1 country for the treatment of cancer. - Participants who have completed 2 years of treatment with pembrolizumab or another anti-PD-1 or anti-PD-L1 antibody, discontinued from that therapy, experienced disease progression, and are then retreated with an anti-PD-1 or anti-PD-L1 antibody will be considered as having had 1 line of anti-PD-1 or anti-PD-L1 therapy. - Adjuvant or neoadjuvant systemic anticancer therapy will not count toward the 2 lines of therapy unless disease recurs during the first year following the start of adjuvant chemotherapy. 4. Participant has measurable disease, that is, 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 disease 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 partici
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: 1. Participant has been previously treated with an anti-PD-1, anti PD- L1 or anti-PD-L2 agent that resulted in permanent discontinuation due to an AE. 2. Participant has been previously treated with an anti-TIM-3 or anti-CTLA-4 agent or docetaxel. 3. Participant has a documented sensitizing EGFR, ALK, or 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. 4. Participant had radiological or clinical disease progression (ie, worsening performance status, clinical symptoms, and laboratory data) =8 weeks after initiation of prior anti-PD-1 or anti-PD-L1 antibody. The clinical disease progression should have been confirmed by a subsequent radiological scan. 5. Participant has received radiation to the lung that is >30 Gy within 6 months prior to the first dose of study treatment. 6. Participant has completed palliative radiotherapy within 7 days prior to the first dose of study treatment. 7. Participant is ineligible if any of the following hepatic characteristics are present: a. Alanine aminotransferase (ALT) >2.5×ULN b. ALT and/or aspartate aminotransferase (AST) >1.5×upper limit of normal (ULN) concomitant with alkaline phosphatase (ALP) >2.5×ULN c. Bilirubin >1×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) Note: Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. 8. Participant has a corrected QT interval (QTc) >450 msec (or QTc >480 msec for participants with bundle branch block). Note the following: -The QTc is the QT interval corrected for heart rate according to Bazett's formula (QTcB), Fridericia's formula (QTcF), and/or another method, machine-read or manually over-read. -The specific formula that will be used to determine eligibility and discontinuation for an individual participant should be determined prior to initiation of the study. In other words, several different formulae cannot be used to calculate the QTc for an individual participant, and then, the lowest QTc value used to include or discontinue the participant from the study. -For purposes of data analysis, QTcB, QTcF, another QT correction formula, or a composite of available values of QTc will be used as specified in the Statistical Analysis Plan (SAP). 9. Participant has had major surgery within 3 weeks prior to the first dose of study treatmentor 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. 10. 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. 11. Participant has known new or progressive brain metastases and/or leptomeningeal metastases.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of cobolimab + dostarlimab + docetaxel relative to docetaxel alone in participants with advanced NSCLC who have progressed on prior anti-PD-1 or anti PD- L1 therapy and chemotherapy To evaluate the efficacy of dostarlimab +docetaxel relative to docetaxel alone in participants with advanced NSCLC who have progressed on prior anti-PD-1 or anti PD- L1 therapy and chemotherapy;Secondary Objective: To evaluate the efficacy of cobolimab + dostarlimab + docetaxel relative to dostarlimab + docetaxel To evaluate additional measures of clinical benefit for cobolimab + dostarlimab +docetaxel relative to docetaxel alone To evaluate additional measures of clinical benefit for dostarlimab + docetaxel relative to docetaxel alone To evaluate additional measures of clinical benefit for cobolimab + dostarlimab +docetaxel relative to dostarlimab + docetaxel To evaluate the safety and tolerability of cobolimab + dostarlimab + docetaxel and dostarlimab + docetaxel vs docetaxel alone;Primary end point(s): efficacy of triplet compared to docetaxel alone-OS defined as survival from the date of randomization to the date of death by any cause doublet compared to docetaxel alone-OS defined as survival from the date of randomization to the date of death by any cause;Timepoint(s) of evaluation of this end point: Up to 44 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): efficacy of the triplet relative to the doublet-OS defined as survival from the date of randomization to the date of death by any cause The study will compare Arm A vs Arm C, Arm B vs Arm C and Arm A vs. Arm B using the following endpoints Confirmed ORR defined as the proportion of participants who have achieved confirmed CR or confirmed PR, evaluated using RECIST v1.1 based on Investigator assessment PFS defined as the length of time until disease progression, from the time of randomization to the earliest date of assessment of disease progression based on RECIST v1.1 by Investigator assessment or death by any cause DOR defined as the time from first documented response (CR/PR) until the time of first documentation of disease progression based on RECIST v 1.1 by Investigator assessment or death, whichever occurs first TTD in lung cancer defined as time from randomization to meaningful deterioration on a composite endpoint of dyspnea, chest pain, and cough, from the EORTC-QLQ-LC13 Change from baseline as assessed by the EORTC-QLQ-C30 and the EORTC-QLQ-LC13 domains The incidence of TEAEs, SAEs, irAEs, TEAEs leading to death, and AEs leading to discontinuation occurring while participants are on treatment or up to 90 days after the last dose of study treatment. Clinical laboratory parameters (hematology, chemistry, thyroid function, and urinalysis), vital signs, ECOG performance status, ECG parameters, physical examinations, and usage of concomitant medications will be collected. ;Timepoint(s) of evaluation of this end point: Up to 44 months From baseline (Day 1) up to 44 months | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Finland, France, Germany, Greece, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Romania, Russian Federation, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trials Help Desk Support
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed