Efficacy Comparison of Cobolimab + Dostarlimab + Docetaxel to Dostarlimab + Docetaxel to Docetaxel Alone in Participants with Advanced NSCLC who Progressed on Prior Anti PD (L)1 Therapy and Chemotherapy (COSTAR LUNG)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited, Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Jan 2021 → ongoing

Decision date (initial)

2024-04-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

GSK Pharma R&D

External identifiers

EU CT number

2023-507475-21-00

EudraCT number

2020-003433-37

ClinicalTrials.gov

NCT04655976

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

"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 objectives 5

1. "To evaluate the efficacy of cobolimab + dostarlimab + docetaxel relative to dostarlimab + docetaxel "
2. To evaluate additional measures of clinical benefit for cobolimab + dostarlimab + docetaxel relative to docetaxel alone
3. To evaluate additional measures of clinical benefit for dostarlimab + docetaxel relative to docetaxel alone
4. To evaluate additional measures of clinical benefit for cobolimab + dostarlimab + docetaxel relative to dostarlimab + docetaxel
5. To evaluate the safety and tolerability of cobolimab + dostarlimab + docetaxel and dostarlimab + docetaxel vs docetaxel alone

Conditions and MedDRA coding

Lung Cancer, Non-Small Cell

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: ‘Sharing Clinical Trial Data’ on the GSK Study Register (www.gsk-studyregister.com). IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months. IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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 anti-PD-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 participant is not eligible. See APPENDIX 1 for the definition of a measurable lesion."
5. "Participant has documented radiological disease progression on prior platinum-based chemotherapy and on prior anti-PD-1 or anti-PD-L1 therapy according to RECIST v1.1."
6. "Participant agrees to submit an archival FFPE tumor tissue specimen that was collected on or after diagnosis of metastatic disease from location(s) not irradiated prior to biopsy. Both tissue block and freshly cut slides are acceptable. If archival tissue is not available, the participant must undergo biopsy prior to study entry. See the Study Reference Manual for further details. a. Participants are also encouraged, but not required, to have a fresh tumor tissue biopsy of a primary or metastatic tumor prior to dosing (samples will be used to enable biomarker analysis). For a full list of Inclusion criteria please refer to the Study Protocol Section 5.1 Inclusion Criteria pg57-61 "

Exclusion criteria 14

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 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."
3. Participant has been previously treated with an anti-TIM-3 or anti-CTLA-4 agent or docetaxel.
4. "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."
5. "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."
6. "Participant has received radiation to the lung that is >30 Gy within 6 months prior to the first dose of study treatment."
7. "Participant has completed palliative radiotherapy within 7 days prior to the first dose of study treatment."
8. "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."
9. "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)."
10. "Participant has had major surgery within 3 weeks prior to 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."
11. "Participant has known new or progressive brain metastases and/or leptomeningeal metastases. Participants who have received prior therapy for their brain metastases and have radiologically 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."
12. "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 an 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."
13. "Participant has an active infection requiring systemic therapy within 1 week prior to the anticipated first dose of study treatment."
14. "Participant has known HIV (positive for HIV-1 or HIV-2 antibodies). For a full list of Exclusion criteria please refer to the Study Protocol Section 5.2 Exclusion Criteria pg61-64"

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. " Efficacy of triplet compared to docetaxel alone-OS defined as survival from the date of randomization to the date of death by any cause. "
2. " Efficacy of doublet compared to docetaxel alone-OS defined as survival from the date of randomization to the date of death by any cause. "

Secondary endpoints 3

1. "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. "
2. "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 -PFS -DOR -TTD -Change from baseline as assessed by the EORTC-QLQ-C30 and the EORTC-QLQ-LC13 domains "
3. "The study will evaluate the safety and tolerability of Arm A and Arm B vs docetaxel alone using the following endpoints: - 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."

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

G S K House, 980 Great West Road 980 Great West Road

City

Brentford

Postcode

TW8 9GS

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 36

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

79 New Oxford Street

City

London

Postcode

WC1A 1DG

Country

United Kingdom

Sponsor responsibilities

Article 77 compliance

Glaxosmithkline Research & Development Limited

Contact point sponsor

Glaxosmithkline Research & Development Limited

Article 77 implementation

Glaxosmithkline Research & Development Limited

Locations

11 EU/EEA countries · 66 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 156 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications