A Phase 1b/2 Study to Evaluate the Efficacy and Safety of Pembrolizumab in Combination with Investigational Agents for the Treatment of Participants With PD-1/L1-refractory Extensive-Stage Small Cell Lung Cancer in Need of Second-Line Therapy (KEYNOTE-B98)
- Conditions
- Extensive-Stage Small Cell Lung CancerMedDRA version: 21.1Level: PTClassification code 10041068Term: Small cell lung cancer extensive stageSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-005628-12-IT
- Lead Sponsor
- MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 80
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
For more Inclusion criteria please see the protocol
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 45
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 35
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 treatmentrelated 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
For more exclusion criteria please see the protocl
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method