A Phase 3 Study of Pembrolizumab (MK-3475) in Combination with Concurrent Chemoradiation Therapy Followed by Pembrolizumab with or without Olaparib (MK-7339), Compared to Concurrent Chemoradiation Therapy in Participants with Newly Diagnosed Treatment-Naïve Limited-Stage Small Cell Lung Cancer (LS-SCLC)

Phase 1

• Conditions: imited-Stage Small Cell Lung Cancer (LS-SCLC); MedDRA version: 21.1Level: LLTClassification code 10041071Term: Small cell lung cancer stage unspecifiedSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-003616-31-FR
• 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: 2020-09-02
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 672

Inclusion Criteria

1.Has pathologically (histologically or cytologically) confirmed SCLC.
2.Has LS-SCLC (Stage I-III, by AJCC 8th Edition Cancer Staging), and can be safely treated with definitive radiation doses.
3.Has no evidence of metastatic disease by whole body PET/CT scan, CT or MRI scans of diagnostic quality of chest, abdomen, pelvis and brain. The process for image collection and transmission to the central imaging vendor can be found in the Site Imaging Manual.
4.Has 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.
5.Has not received prior treatment (chemotherapy or radiotherapy or surgery resection) of LS-SCLC.
6.Is not expected to require tumor resection during the course of the study.
7.Must submit a pre-treatment tumor tissue sample. Any available tumor tissue sample can be submitted: histologic (ie, core, incisional, or excisional biopsy) or cytologic sample (if tissue sample unavailable). The sample should be submitted before or within 4 weeks after randomization; however, participants may be enrolled into the study before the pre-treatment tissue sample is submitted.
8.Has ECOG Performance score 0 or 1 assessed within 7 days prior to the first administration of study intervention.
9.Has a life expectancy of at least 6 months.
10.Has adequate PFT defined as an FEV1 >50% of predicted normal volume and a DLCO >40% of predicted normal value. Participants for whom DLCO measurements are not available will be deemed to have adequate oxygen transfer if pulse oximetry (O2 saturation) =90% room air.
11.Has adequate organ function; all screening laboratory tests should be performed within 10 days prior to initiation of study intervention.
12.Male participants are eligible to participate if they agree to the following during the intervention period and for at least 180 days after the last dose of study intervention:
-Refrain from donating sperm
PLUS either:
-Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
OR
-Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) 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.
13.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 a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 180 days after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
-A W

Exclusion Criteria

1.Has extensive stage disease, defined as stage IV (T any, N any M1a/b), or T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan.
2.Has history, current diagnosis, or features suggestive of MDS/AML.
3.Has had documented weight loss >10% (from baseline) in the preceding 3 months.
4.Has a radiation treatment plan that is likely to encompass a volume of whole lung (total lung V20-GTV) receiving >20 Gy in total (V20) of more than 35% of lung volume.
5.Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.
6.Has received prior therapy with olaparib or with any other PARP inhibitor.
7.Had major surgery <4 weeks prior to the first dose of study intervention (except for placement of vascular access).
8.Is expected to require any other form of antineoplastic therapy, while on study.
9.Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention.
10.Has received colony-stimulating factors within 28 days prior to the first dose of study intervention.
11.Is currently receiving either strong (phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort) or moderate inducers of CYP3A4 that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 5 weeks for pentobarbital and 3 weeks for other agents.
12.Is currently receiving either strong or moderate inhibitors of cytochrome P450 (CYP)3A4 that cannot be discontinued for the duration of the study. The required washout period prior to starting olaparib is 2 weeks.
13.Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
14.Has uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg, unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolyte disturbances, etc.), or participants with congenital long QT syndrome.
15.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.
16.Has a known additional malignancy that is progressing or has required active treatment within the past 5 years.
17.Has severe hypersensitivity (= Grade 3) to study intervention and/or any of its excipients.
18.Has an active autoimmune disease that has required systemic treatment in 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 and is allowed.
19.Has a known history of, or active, neurologic paraneoplastic syndrome.
20.Has a history of (non-infectious) pneumonitis/interstitial lung disease that requires steroids or has current pneumonitis/interstitial lung disease. Lymphangitic spread of the LS-SCLC is not exclusionary.
21.Has an active infection requiring systemic therapy.
22.Has a known history of human immunodeficiency virus

Study & Design

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