Placebo-controlled, Study of Concurrent Chemoradiation Therapy With Pembrolizumab Followed by Pembrolizumab and Olaparib in Newly Diagnosed Treatment-Naïve Limited-Stage Small Cell Lung Cancer (LS-SCLC) (MK 7339-013/KEYLYNK-013)

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

9 Dec 2020 → ongoing

Decision date (initial)

2023-12-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC · AstraZeneca

External identifiers

EU CT number

2023-504959-27-00

EudraCT number

2019-003616-31

WHO UTN

U1111-1290-4870

ClinicalTrials.gov

NCT04624204

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Therapy, Pharmacogenomic, Efficacy, Pharmacogenetic

1. To compare progression free survival (PFS) per RECIST 1.1 as assessed by BICR
2. To compare overall survival (OS)

Secondary objectives 9

1. To evaluate the safety and tolerability (ST) of concurrent chemoradiation therapy (CCT) with pembrolizumab (pembro) followed by pembro plus olaparib (Gp B) compared to CCT alone (Gp C)
2. To evaluate ST of CCT with pembro followed by pembro (Gp A) compared to Gp C
3. To compare Gp B to Gp C with respect to objective response rate (ORR) as assessed by BICR per RECIST 1.1
4. To compare Gp A to Gp C with respect to ORR as assessed by BICR per RECIST 1.1
5. To compare Gp B to Gp C with respect to duration of response (DOR) as assessed by BICR per RECIST 1.1
6. To compare Gp A to Gp C with respect to DOR as assessed by BICR per RECIST 1.1
7. To evaluate change from baseline (CFB) (at Cycle 1) and time to true deterioration (TTD) in global health status/quality of life (QoL) in Gp B compared to Gp C
8. To evaluate CFB (at Cycle 1) and the TTD in QoL in Gp A compared to Gp C
9. To evaluate the effect of programmed cell death ligand 1 (PD-L1) expression levels on OR, DOR, PFS, and OS

Conditions and MedDRA coding

Participants with Limited Stage-Small Cell Lung Cancer, who have received no prior anticancer therapy for their disease.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Has pathologically (histologically or cytologically) confirmed Small Cell Lung Cancer (SCLC). Note: Participants with histology showing a mixed tumor with small cell and non-small cell elements are not eligible
2. Has Limited-Stage 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 positron emission tomography /computed tomography (PET/CT scan), CT or magnetic resonance imaging (MRI) scans
4. Has at least 1 lesion that meets the criteria for being measurable, as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
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 (formalin-fixed, paraffin embedded blocks are preferred to slides) including cytologic sample, if tissue sample unavailable
8. Has Eastern Cooperative Oncology Group (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 organ function
11. Male and female participants who are not pregnant and of childbearing potential must follow contraceptive guidance during the treatment period and for the time needed to eliminate each study intervention
12. Male and female participants who are at least 18 years of age at the time of signing the information consent
13. Male participants must refrain from donating sperm during the treatment period and for the time needed to eliminate each study intervention
14. Abstains from breastfeeding during the study intervention period and for at least the following period after the last study intervention: - Pembrolizumab: 120 days - Olaparib: 7 days

Exclusion criteria 12

1. Has history, current diagnosis, or features suggestive of myelodysplastic syndrome/ acute myeloid leukemia (MDS/AML)
2. Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PDL1), or anti- programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
3. Has received prior therapy with olaparib or with any other polyadenosine 5'diphosphoribose (polyADP ribose) polymerization (PARP) inhibitor
4. Had major surgery <4 weeks prior to the first dose of study intervention (except for placement of vascular access)
5. 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
6. 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
7. Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
8. Has severe hypersensitivity (≥ Grade 3) to study intervention and/or any of its excipients
9. Has an active autoimmune disease that has required systemic treatment in past 2 years
10. Has a history of (non-infectious) pneumonitis/interstitial lung disease that requires steroids
11. Has an active infection requiring systemic therapy
12. Has a known history of human immunodeficiency virus (HIV) infection or Hepatitis B or known active Hepatitis C virus infection

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1): the time from randomization to progression or death due to any cause, whichever occurs first
2. Overall Survival (OS): the time from randomization to death due to any cause

Secondary endpoints 18

1. Number of Participants Experiencing an Adverse Events (AEs)
2. Number of Participants Discontinuing Study Treatment Due to Adverse Events (AEs)
3. Objective Response (OR): complete response (CR) or partial response (PR)
4. Duration of Response (DOR): the time from the earliest date of first documented evidence of confirmed CR or PR until the earliest date of disease progression or death from any cause, whichever comes first
5. Change from Baseline at Cycle 1 in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status / Quality of Life (Items 29 & 30) Scale Score
6. Change from Baseline at Cycle 1 in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score
7. Change from Baseline at Cycle 1 in EORTC QLQ-LC13 Chest Pain (Item 10) Scale Score
8. Change from Baseline at Cycle 1 in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score
9. Change from Baseline at Cycle 1 in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score
10. Time to True Deterioration (TTD) in EORTC QLQ-C30 Global Health Status / Quality of Life (Items 29 & 30) Scale Score
11. Time to True Deterioration (TTD) in Cough (LC13/Item 1) Scale Score
12. Time to True Deterioration (TTD) in Chest Pain (LC13/Item 10) Scale Score
13. Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score
14. Time to True Deterioration (TTD) in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Score
15. Objective Response (OR, according to RECIST 1.1 by BICR) assessed by programmed cell death ligand 1 (PD-L1) expression levels
16. Duration of Response (DOR, according to RECIST 1.1 by BICR) assessed by programmed cell death ligand 1 (PD-L1) expression levels
17. Progression-free Survival (PFS, according to RECIST 1.1 by BICR) assessed by programmed cell death ligand 1 (PD-L1) expression levels
18. Overall Survival (OS) assessed by programmed cell death ligand 1 (PD-L1) expression levels

Investigational products

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

Test 3

Placebo 2

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

Kumar Rajagopalan

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Kumar Rajagopalan

Third parties 9

Locations

11 EU/EEA countries · 45 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 152 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