Extensive-Stage Small Cell Lung Cancer MedDRA version: 21.1 Level: PT Classification code 10041068 Term: Small cell lung cancer extensive stage System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: MK-1308/MK-3475
Product Code: MK-1308A
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Quavonlimab
Current Sponsor code: MK-1308
Other descriptive name: MK-1308
Concentra
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has histologically or cytologically confirmed diagnosis of ES-SCLC in need of second-line therapy 2. Participants must have progressed on or after treatment with an anti-PD-1/L1 mAb administered as part of first-line platinum-based systemic therapy for ES-SCLC. PD-1/L1 checkpoint inhibitor treatment progression is defined by meeting ALL of the following criteria: a. Has received at least 2 doses of an anti-PD-1/L1 mAb b. Has demonstrated radiographic disease progression during or after an anti-PD-1/L1 mAb as defined by investigator c. Disease progression has been documented within 12 weeks from the last dose of an anti-PD-1/L1 mAb 3. Has extensive-stage SCLC defined as Stage IV by the American Joint Committee on Cancer, Eighth Edition 4. Has received 1 prior line of systemic therapy for SCLC. Study intervention will treat second-line ES-SCLC 5. Is male or female, at least 18 years of age at the time of providing documented informed consent 6. Male participants are eligible to participate if they agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows: - Lenvatinib – 7 days - Pembrolizumab, MK-1308A, MK-4830, MK-4280A – no contraception measures required • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent OR • Must agree to use contraception unless confirmed to be azoospermic as detailed below: - Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant • Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies 7. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: • Is not a WOCBP OR • Is WOCBP and using a contraceptive method that is highly effective, with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle, during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows: - Lenvatinib – 30 days - Pembrolizumab, MK-1308A, MK-4830, MK-4280A – 120 days The investigator should evaluate the potential for contraceptive method failure in relationship to the first dose of study intervention - A WOCBP must have a negative highly sensitive pregnancy test within 24 hours before the first dose of study intervention - If a urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive - The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy - Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies 8. The participant (or legally acceptable representative) has provided documented informed consent for the study 9. Has m
Exclusion criteria
Exclusion criteria: 1. Has had major surgery within 3 weeks before first dose of study interventions 2. Has a preexisting =Grade 3 gastrointestinal or non-gastrointestinal fistula 3. Has urine protein =1 g/24 hours 4. Has a LVEF below the institutional (or local laboratory) normal range, as determined by MUGA or ECHO 5. Prolongation of QTcF interval to >480 ms 6. 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 7. Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks before the first dose of study intervention 8. Has gastrointestinal malabsorption or any other condition that might affect oral study intervention absorption 9. Has serious nonhealing wound, ulcer, or bone fracture within 28 days before the start of study intervention 10. Has any major hemorrhage or venous thromboembolic events within 3 months before the start of study intervention. Participants with venous thrombosis diagnosed more than 3 months before the start of study intervention must be on stable doses of anticoagulants 11. Has a history of inflammatory bowel disease 12. Has a history of a gastrointestinal perforation within 6 months before the start of study intervention 13. Has a known history of, or active, neurologic paraneoplastic syndrome 14. Is considered a poor medical risk due to a serious, uncontrolled medical disorder or nonmalignant systemic disease 15. Has received prior therapy with an RTK inhibitor or anti-CTLA-4, anti-ILT-4, or anti- LAG-3 agents 16. Has received prior therapy with an anti-PD-1/L1 agent and was permanently discontinued from that treatment due to a treatment-related AE 17. Has received prior systemic anticancer therapy including investigational agents within 4 weeks before start of study intervention 18. Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease 19. Has received lung radiation therapy >30 Gy within 6 months before the first dose of study intervention 20. Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed 21. 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 intervention 22. Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation 23. Has symptomatic ascites, pleural effusion, or pericardial effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoracoor paracentesis) is eligible 24. 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 intervention 25. Has a known additional malignancy that is progressing or has required active treatment within the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the safety and tolerability of investigational treatment combinations based on the proportion of participants with adverse events 2. To estimate the objective response rate as assessed by blinded independent central review per RECIST 1.1;Secondary Objective: 1. To evaluate progression-free survival as assessed by blinded independent central review according to RECIST 1.1 2. To evaluate duration of response as assessed by blinded independent central review according to RECIST 1.1;Primary end point(s): 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);Timepoint(s) of evaluation of this end point: 1. Up to 21 days in Cycle 1 (Cycle 1 = 21 days) 2. Up to approximately 60 months 3. Up to approximately 60 months 4. Up to approximately 60 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 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);Timepoint(s) of evaluation of this end point: 1. Up to approximately 60 months 2. Up to approximately 60 months | — |
Countries
Australia, Austria, Canada, Germany, Hungary, Israel, Italy, Korea, Republic of, Poland, Russian Federation, Spain, Switzerland, United States
Outcome results
None listed