Substudy to test investigational agents with pembrolizumab in combination with chemotherapy in treatment-naïve NSCLC in a rolling arm design

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Oct 2020 → 18 Sep 2025

Decision date (initial)

2024-01-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-506932-33-00

EudraCT number

2020-001626-56

WHO UTN

U1111-1294-6474

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacoeconomic, Pharmacodynamic, Pharmacokinetic, Diagnosis, Therapy, Safety, Pharmacogenetic

1. To estimate the objective response rate (ORR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)

Secondary objectives 2

1. To estimate Progression Free Survival (PFS) as assessed by the investigator according to RECIST 1.1
2. To evaluate the safety and tolerability of investigational treatment combinations based on proportion of adverse events

Conditions and MedDRA coding

non-small cell lung cancer

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Has histologically- or cytologically-confirmed diagnosis of Stage IV squamous or nonsquamous non-small cell lung cancer (NSCLC)
2. Participants with nonsquamous NSCLC who are not eligible for an approved targeted therapy
3. Is able to provide archival tumor tissue sample collected either within 5 years or within the interval from completion of last treatment but before entering the screening period or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated obtained within 90 days of treatment initiation
4. Has not received prior systemic treatment for their metastatic NSCLC
5. Is able to complete all screening procedures within the 35-day screening window
6. Has adequate organ function within 10 days of initiation of study treatment
7. Male participants must agree to use contraception and should refrain from donating sperm during the treatment period and for at least 120 days after the last dose of pembrolizumab and for at least 180 days after the last dose of chemotherapy
8. Female participants must not be pregnant or breastfeeding, and at least one of the following conditions apply: Not a woman of childbearing potential (WOCBP), OR A WOCBP who agrees to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab and for at least 180 days after the last dose of chemotherapy

Exclusion criteria 31

1. Has a diagnosis of small cell lung cancer
2. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or in any other form of immunosuppressive therapy within 7 days before the first dose of the study treatment
3. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
4. Has a known active central nervous system (CNS) metastases and/or carcinomatous meningitis
5. Has an active autoimmune disease that has required systemic treatment in the past 2 years
6. Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
7. Has an active infection requiring systemic therapy
8. Has a clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study treatment administration, or New York Heart Association Class III or IV congestive heart failure
9. Has a known history of HIV infection
10. Has a known history of Hepatitis B or known active Hepatitis C virus infection
11. Has had major surgery <3 weeks before the first dose of study treatment
12. Is expected to require any other form of antineoplastic therapy while on study
13. Has symptomatic ascites or pleural effusion (if receiving pemetrexed; Alimta®, Eli Lilly)
14. Has a history or current evidence of gastrointestinal (GI) condition (e.g. inflammatory bowel disease, Crohn’s disease, ulcerative colitis) or impaired liver function or diseases that in the opinion of the investigator may significantly alter the absorption or metabolism of oral medications
15. Is getting chemotherapy and has clinically active diverticulitis, intra-abdominal abscess, GI obstruction, or peritoneal carcinomatosis
16. Has preexisting neuropathy that is moderate in intensity
17. Has received prior systemic cytotoxic chemotherapy or other targeted or biological antineoplastic therapy for metastatic disease
18. Has received prior therapy with an anti-programmed cell death-1 (PD-1), anti-programmed cell death-ligand 1 (PD-L1), or anti-PD-L2 agent or prior therapy targeting other immunoregulatory receptors or mechanisms
19. Is currently receiving either strong or moderate inhibitors of cytochrome P450 3A4 (CYP3A4) or cytochrome P450 2C8 (CYP2C8) that cannot be discontinued for the duration of the study
20. Is currently receiving strong or moderate inducers of CYP3A4 or CYP2C8 that cannot be discontinued for the duration of the study
21. Is unable to interrupt aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs), other than aspirin dose less than or equal to 1.3 gm/day for a 5-day period (8-day period for long acting agents such as peroxicam), for participants who will receive pemetrexed
22. Is unable or unwilling to take folic acid or vitamin B12 supplementation, for participants who will receive pemetrexed
23. Has a known sensitivity to any component of carboplatin, paclitaxel, pemetrexed or any of their excipients
24. Has received prior radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study treatment
25. Has received a live vaccine within 30 days before the first dose of study treatment. Any licensed COVID-19 vaccine (including for Emergency Use) in a particular country is allowed as long as they are messenger ribonucleic acid (mRNA) vaccines, adenoviral vaccines, or inactivated vaccines. Investigational vaccines (ie, those not licensed or approved for Emergency Use) are not allowed
26. Has received any prior immunotherapy and was discontinued from that treatment due to a severe or worse immune-related adverse event (irAE)
27. Has had chemotherapy or biological cancer therapy within 4 weeks before the first dose of study treatment or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the AEs due to cancer therapeutics administered more than 4 weeks before the first dose of study treatment (including participants who had previous immunomodulatory therapy with residual irAEs)
28. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study treatment
29. Previously had a severe hypersensitivity reaction to treatment with monoclonal antibodies (including pembrolizumab) and/or any of their excipients
30. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
31. Has had an allogenic tissue/solid organ transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

Secondary endpoints 3

1. Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
2. Number of Participants Who Experience One or More Adverse Events (AE)
3. Number of Participants Who Discontinue Treatment Due to an Adverse Event

Investigational products

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

Test 6

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Azadeh Namakydoust

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Azadeh Namakydoust

Third parties 10

Locations

4 EU/EEA countries · 12 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 51 files

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

Application history

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