A clinical study of pembrolizumab with other study treatments in people with refractory lung cancer (MK-3475-B98)

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

23 Aug 2021 → ongoing

Decision date (initial)

2024-04-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DAIICHI SANKYO COMPANY, LIMITED · Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-507687-38-00

EudraCT number

2020-005628-12

WHO UTN

U1111-1296-5646

ClinicalTrials.gov

NCT04938817

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy, Pharmacokinetic, Pharmacogenomic

1. To evaluate the safety and tolerability of investigational treatment(s) and treatment combinations based on the proportion of participants with adverse events
2. To estimate the ORR per RECIST 1.1 as assessed by BICR

Secondary objectives 2

1. To evaluate PFS per RECIST 1.1 as assessed by BICR
2. To evaluate DOR per RECIST 1.1 as assessed by BICR

Conditions and MedDRA coding

Participants with extensive-stage small cell lung cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Arms A-E: Has histologically or cytologically confirmed diagnosis of ES-SCLC in need of second-line therapy
2. Arms A-E: Has progressed on or after treatment with an anti-programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PD-L1) monoclonal antibody (mAb) administered as part of first-line platinum-based systemic therapy for ES-SCLC
3. Arms A-E: Has ES-SCLC defined as Stage IV (T any, N any, M1a/b/c) by the American Joint Committee on Cancer, Eighth Edition
4. Arms A-E: Has received 1 prior line of systemic therapy for small cell lung cancer (SCLC)
5. Arms A-D: Male participants must be abstinent from heterosexual intercourse or agree to use contraception during treatment for at least 7 days after the last dose of lenvatinib. No contraception is required if the participant is receiving pembrolizumab, pembrolizumab/quavonlimab, MK-4830, or favezelimab/pembrolizumab
6. Arms A-D: Female participants are not pregnant or breastfeeding and are not a woman of childbearing potential (WOCBP) or if are a WOCBP, are abstinent from heterosexual intercourse or are using contraception during the intervention period and for at least 120 days after the last dose of pembrolizumab, pembrolizumab/quavonlimab, MK-4830, or favezelimab/pembrolizumab or 30 days after the last dose of lenvatinib, whichever occurs last
7. Arms A-D: Female participants must abstain from breastfeeding during the intervention period and for at least 120 days after the last dose of pembrolizumab, pembrolizumab/quavonlimab, MK-4830, or favezelimab/pembrolizumab or 7 days after the last dose of lenvatinib, whichever occurs last
8. Arms A-E: A WOCBP must have a negative highly sensitive pregnancy test within 24 hours (for a urine test) or 72 hours (for a serum test) before the first dose of study treatment
9. Arms A-E: Has measurable disease per RECIST 1.1 as assessed by local site investigator/radiology and verified by BICR
10. Arms A-E: Has submitted an archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated where such sample exists
11. Arms A-E: Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before allocation/randomization
12. Arms A-E: Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization
13. Arms A-E: Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
14. Arms A-D: Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 millimeters of mercury (mm Hg) with no change in antihypertensive medications within 1 week before allocation/randomization
15. Arms A-E: Has a predicted life expectancy of >3 months
16. Arm E: If capable of producing sperm, the participant agrees to refrain from donating sperm and abstain from penile-vaginal intercourse or use a penile/external condom when having penile-vaginal intercourse with a nonparticipant of childbearing potential who is not currently pregnant. The length of time required to continue contraception for the study intervention R-Dx-d is 120 days
17. Arm E: A person of childbearing potential (POCBP) must use a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or if they adhere to penile-vaginal intercourse abstinence as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least the time needed to eliminate the study intervention after the last dose of study intervention. In addition, the participant agrees not to donate eggs (ova, oocytes) to others or freeze/store eggs during this period for the purpose of reproduction. The length of time required to continue contraception for the study intervention R-Dx-d is 210 days

Exclusion criteria 34

1. Arms A-D: Has had major surgery within 3 weeks before first dose of study treatment
2. Arms A-D: Has a preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
3. Arms A-D: Has clinically significant cardiovascular disease or major arterial thromboembolic event within 12 months before first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability
4. Arms A-D: Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks before the first dose of study treatment
5. Arms A-D: Has gastrointestinal malabsorption or any other condition that might affect oral study intervention absorption
6. Arms A-D: Has serious nonhealing wound, ulcer, or bone fracture within 28 days before the start of study treatment
7. Arms A-D: Has any major hemorrhage or venous thromboembolic events within 3 months before the start of study treatment
8. Arms A-D: Has a history of inflammatory bowel disease
9. Arms A-D: Has a history of a gastrointestinal perforation within 6 months before the start of study treatment
10. Arms A-D: Has a known history of, or active, neurologic paraneoplastic syndrome
11. Arms A-D: Has received prior therapy with a receptor tyrosine kinase (RTK) inhibitor or anti- cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), anti-immunoglobulin-like transcript (ILT)-4, or anti-lymphocyte-activation gene 3 (LAG-3) agents
12. Arms A-D: Has received prior therapy with an anti-PD-1/L1 agent and was permanently discontinued from that treatment due to a treatment-related adverse event
13. Arms A-E: Has received prior systemic anticancer therapy including investigational agents within 4 weeks before start of study treatment
14. Arms A-E: Has received prior radiotherapy within 2 weeks of start of study treatment
15. Arms A-E: Has received lung radiation therapy >30 Gray (Gy) within 6 months before the first dose of study treatment
16. Arms A-E: Has received a live or live attenuated vaccine within 30 days before the first dose of study treatment
17. Arms A-D: Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
18. Arms A-D: Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
19. Arms A-D: Has symptomatic ascites, pleural effusion, or pericardial effusion
20. Arms A-D: 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 prior the first dose of study treatment
21. Arms A-E: Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
22. Arms A-E: Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with brain metastases may participate only if they satisfy all of the following: completed treatment (e.g., whole brain radiation treatment, stereotactic radiosurgery, or equivalent) ≥14 days before the first dose of study intervention; have no evidence of new or enlarging brain metastases confirmed by post-treatment repeat brain imaging (using the same modality) performed ≥4 weeks after pretreatment brain imaging; and are neurologically stable without the need for steroids for ≥7 days before the first dose of study intervention as per local site assessment. Participants with untreated brain metastases will be allowed if they are asymptomatic, the investigator determines there is no immediate CNS-specific treatment required, there is no significant surrounding edema, and the brain metastases are of 5 millimeter (mm) or less in size and 3 or less in number.
23. Arms A-E: Has a history of severe hypersensitivity reaction (≥Grade 3) to any study treatment and/or any of its excipients
24. Arms A-E: Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid)
25. Arms A-E: Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
26. Arms A-E: Has an active infection requiring systemic therapy
27. Arms A-D: Has a known history of Human Immunodeficiency Virus (HIV) infection
28. Arms A-D: Has concurrent active HBV or HCV
29. Arms A-D: Has progressive disease as initial response to first-line systemic chemotherapy in combination with PD-1/L1 inhibitor for ES-SCLC
30. Arms A-D: Has had an allogenic tissue/solid organ transplant
31. Arm E: Received prior treatment with a CDH6-targeted agent or an ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor (eg, trastuzumab deruxtecan, datopotamab deruxtecan)
32. Arm E: Has received an investigational agent or has used an investigational device within 4 weeks (or 5 half-lives, whichever is shorter) prior to study intervention administration
33. Arm E: Has Chronic steroid treatment (>10 mg/day prednisone [or equivalent] per day), except for inhaled steroids for asthma or COPD, mineralocorticoids (e.g., fludrocortisone) for participants with orthostatic hypotension, topical steroids for mild skin conditions, low-dose supplemental corticosteroids for adrenocortical insufficiency, Premedication for treatment groups and/or premedication in case of any hypersensitivity, or intra-articular steroid injections
34. Arm E: Is an HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
2. Number of Participants Who Experience at Least One Adverse Event (AE)
3. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
4. Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)

Secondary endpoints 2

1. Progression-free Survival (PFS) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
2. Duration of Response (DOR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)

Investigational products

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

Test 7

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

Haichuan Hu​

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Haichuan Hu​

Third parties 7

Locations

5 EU/EEA countries · 11 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 33 files

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

Application history

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