Phase 3 Study of Pembrolizumab with or without Maintenance Olaparib in 1L ES SCLC

Phase 1

• Conditions: Extensive Stage Small Cell Lung Cancer; MedDRA 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: EUCTR2018-004843-22-HU
• Lead Sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co.,Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-10-25
• Last Update Posted: 13 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 699

Inclusion Criteria

1. Have a documented new diagnosis of SCLC by histology or cytology from brushing, washing, or needle aspiration of a defined lesion. Participants who do not have histology samples (defined as core or incisional biopsy, or resections) will need to undergo a new biopsy to provide a tissue sample
2. Have extensive stage disease defined as Stage IV (T any, N any, M 1a/b/c) by the American Joint Committee on Cancer, Eighth Edition
3. Have at least 1 lesion that meets the criteria for being measurable, as defined by RECIST 1.1, and is appropriate for selection as a target lesion, as determined by local site investigator/radiology review. Lesions that appear measurable, but have undergone palliative irradiation, cannot be target lesions
4. Have provided archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin-embedded tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue
5. Have an ECOG Performance Status of 0 to 1 assessed within 7 days prior to the administration of study intervention
6. Have a life expectancy of at least 3 months
7. Have adequate organ function; all screening laboratory tests should be performed within 10 days prior to initiation of study intervention
8. Be at least 18 years of age at the time of signing the informed consent
9. A male participant must agree to use contraception during the treatment period and for at least 180 days following the last dose of pembrolizumab and olaparib or at least 180 days following the last dose of cytotoxic chemotherapy
10. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
- Not a woman of childbearing potential (WOCBP)
OR
- A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 180 days following the last dose of pembrolizumab and olaparib or at least 180 days following the last dose of cytotoxic chemotherapy
11. Has (or legally acceptable representative if applicable) provided written informed consent/assent for the study. The participant may also provide consent/assent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research

Additional Criteria Applicable to Maintenance Phase Only – Prior to Randomization
12. Have a CR/PR or stable disease of their SCLC after completion of the study-specified Induction Phase, as determined by central imaging review
13. Have an ECOG score of 0 or 1
14. All AEs (except alopecia, Grade 2 fatigue, and endocrine-related AEs Grade =2 requiring treatment or hormone replacement) resolved to Grade =1 or baseline following Induction Phase treatment
15. Have adequate organ function
16. Are not taking medications or vaccinations specifically prohibited in the Exclusion Criteria
17. Are not pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting from the pre-randomization visit through 180 days after the last dose of study intervention
18. Have not withdrawn consent to continue treatment
19. Continue to derive clinical benefit from study participation according to investigator’s discretion
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 366
F.1.3 E

Exclusion Criteria

1. Has received prior systemic therapy for the treatment of SCLC
2. Is expected to require any other form of antineoplastic therapy for SCLC, including radiation therapy, while on study
3. Has a known history of interstitial lung disease. Lymphangitic spread of the SCLC is not exclusionary
4. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
5. Has a known central nervous system (ie, brain and/or spinal cord) metastases and/or carcinomatous meningitis
6. Has had major surgery within 3 weeks of starting study intervention or has not recovered from any effects of any major surgery
7. Has a known additional malignancy that is progressing or requires active treatment
8. Has a known hypersensitivity to the components or excipients of cisplatin, carboplatin, etoposide, or olaparib
9. 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
10. Has active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
11. Has a known history of, or active, neurologic paraneoplastic syndrome
12. Has severe hypersensitivity (Grade =3) to pembrolizumab and/or any of its excipients
13. Has active infection requiring systemic therapy
14. Has a known history of HIV infection. No HIV testing is required unless mandated by local health authority
15. Has a known history of hepatitis B (defined as hepatitis B surface antigen reactive) or known active hepatitis C virus (defined as hepatitis C virus RNA [qualitative] is detected) infection
16. Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis)
17. Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible
18. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the Screening visit through 180 days after the last dose of study intervention
19. Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
20. Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML
21. Has received colony-stimulating factors (eg, granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor or recombinant erythropoietin) within 28 days prior to the first dose of study intervention
22. Is considered a poor medical risk due to a serious, uncontrolled medical disorder or nonmalignant systemic disease. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, or superior vena cava syndrome
23. Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, malabsorption)
24. Has received a live vaccine within 30 days prior to

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified