Substudy to test investigational agents in combination with pembrolizumab in patients with PD-(L)1 refractory 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 → 29 May 2025

Decision date (initial)

2024-01-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-506934-56-00

EudraCT number

2020-001629-29

WHO UTN

U1111-1294-6589

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

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 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 9

1. Has a histologically- or cytologically-confirmed diagnosis of Stage IV squamous or non-squamous NSCLC.
2. Has non-squamous NSCLC and is 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. Have progressed on treatment with an anti-PD-(L)1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies
5. Have progressive disease (PD) during/after platinum doublet chemotherapy
6. Is able to complete all screening procedures within the 35-day screening window
7. Male participants must agree to use contraception and refrain from donating sperm during the treatment period and for at least 120 days after the last dose of study treatment
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 study treatment
9. Has adequate organ function within 10 days of initiation of study treatment

Exclusion criteria 21

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 any other form of immunosuppressive therapy within 7 days before the first dose of study treatment
3. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
4. Has 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 clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study treatment, or New York Heart Association Class III or IV congestive heart failure
9. Has a known history of Human Immunodeficiency Virus (HIV) infection
10. Has a known history of Hepatitis B or known active Hepatitis C virus infection
11. Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study
12. Has had major surgery <3 weeks before the first dose of study treatment
13. Has received prior radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study treatment
14. 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
15. Has received any prior immunotherapy and was discontinued from that treatment due to a severe or worse immune-related adverse event (irAE)
16. 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)
17. 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
18. Has participated in Substudies 1 or 2
19. Has had a severe hypersensitivity reaction to treatment with monoclonal antibodies (including pembrolizumab) and/or any of their excipients
20. 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
21. 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 (AEs)
3. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

Investigational products

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

Test 5

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 9

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 58 files

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

Application history

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