Phase 3 Study of Pembrolizumab with or without Maintenance Olaparib in First-Line Metastatic Squamous NSCLC

• Register: EUCTR
• Last refreshed on: 16 November 2020
• Main ID: EUCTR2018-004721-88-GB
• Date of registration: 16/05/2019
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: Phase 3 Study of Pembrolizumab with or without Maintenance Olaparib in First-Line Metastatic Squamous NSCLC
• Scientific title: A Phase 3 Study of Pembrolizumab in Combination with Carboplatin/Taxane (Paclitaxel or Nab-paclitaxel) Followed by Pembrolizumab with or without Maintenance Olaparib in the First-line Treatment of Metastatic Squamous Non-small Cell Lung Cancer (NSCLC) - Pembrolizumab with or without olaparib in metastatic squamous NSCLC
• Date of first enrolment: 08/07/2019
• Target sample size: 735
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-004721-88
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Brazil, Canada, Colombia, Czechia, France, Germany, Hungary, Japan, Korea, Republic of, Mexico, Netherlands, Peru, Poland, Puerto Rico, Romania, Spain, Sweden, Switzerland, Thailand, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Global Clinical Trial Operations
• Affiliation: Merck Sharp & Dohme (UK) Ltd.

• Name: Global Clinical Trial Operations
• Affiliation: Merck Sharp & Dohme (UK) Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
- Have a histologically or cytologically confirmed diagnosis squamous NSCLC. Patients with mixed histology (eg, adenosquamous) are allowed if there is squamous component in the specimen
- Have stage IV (T any, N any, M1a, M1b, or M1c as per AJCC 8th edition) squamous NSCLC
- Have measurable disease based on RECIST 1.1, as determined by the local site investigator/radiology assessment. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
- Have not received prior systemic treatment for their advanced/metastatic NSCLC. Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of metastatic disease
- Have provided archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status assessed within 7 days prior to the administration of study intervention
- Have a life expectancy of at least 3 months
- Has adequate organ function; all screening laboratory tests should be performed within 10 days prior to initiation of study treatment
- Be at least 18 years of age on day of signing informed consent
- A male participant must agree to use contraception and refrain from donating sperm 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
- 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
- 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 trial without participating in Future Biomedical Research
- Has a CR/PR or stable disease of their NSCLC as determined by central imaging review after completion of study-specified Induction Phase
- Have an ECOG performance status score of 0 or 1
- 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.
- Have adequate organ function, as indicated by the laboratory values in Table 3 above.
- Are not taking medications or vaccinations specifically prohibited in the Exclusion Criteria (Section 5.2).
- 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.
- Have not withdrawn consent to continue treatment.
- Continue to derive clinical benefit from study participation according to investigator’s discretion.
Are the trial subjects under 18? no
Number of su
Exclusion criteria:
- Non-squamous histology NSCLC
- Additional malignancy progressing or progressed within the past 3 years requiring active treatment
- Central nervous system (CNS) metastases and/or carcinomatous meningitis.
Participants with previously treated brain metastases may participate provided they are clinically stable for at least 2 weeks and, have no evidence of new or enlarging brain metastases, and also are off steroids 3 days prior to dosing with study medication
- Autoimmune disease that has required systemic treatment in the past 2 years
- Immunodeficiency or receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or other immunosuppressive therapy within 7 days prior to first dose
- History of (noninfectious) pneumonitis requiring systemic steroids, interstitial lung disease
- Known history of active tuberculosis, HIV infection, HBV infection, or active HCV infection
- Current pneumonitis
- Prior treatment with olaparib or any other PARP inhibitor
- Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2 agent, or agent directed to another stimulatory or co-inhibitory T cell receptor
- Prior systemic chemotherapy or other targeted or biological antineoplastic therapy for metastatic disease
- Is currently receiving either strong or moderate inducers of CYP3A4 that cannot be discontinued for the duration of the study.





Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Metastatic Squamous Non-small Cell Lung Cancer (NSCLC)
MedDRA version: 21.1 Level: LLT Classification code 10029514 Term: Non-small cell lung cancer NOS System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: PEMBROLIZUMAB
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Trade Name: KEYTRUDA (pembrolizumab, MK-3475)
Product Name: KEYTRUDA (pembrolizumab, MK-3475)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-

Product Name: Olaparib
Product Code: MK-7339
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: OLAPARIB
CAS Number: 763113-22-0
Current Sponsor code: MK-7339
Other descriptive name: OLAPARIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Olaparib
Product Code: MK-7339
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: OLAPARIB
CAS Number: 763113-22-0
Current Sponsor code: MK-7339
Other descriptive name: OLAPARIB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): 1.Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
2.Overall survival (OS)

Secondary Objective: 1.To evaluate the safety and tolerability of pembrolizumab plus maintenance olaparib compared to pembrolizumab plus placebo in participants with stage IV squamous non-small cell lung cancer (NSCLC) with stable disease (SD), partial response (PR), or complete response (CR) following induction treatment with pembrolizumab combined with carboplatin and a taxane (paclitaxel or nab paclitaxel)
2.To evaluate the change from baseline (at randomization) and the time to true deterioration (TTD) in global health status/quality of life (QoL), cough, chest pain, dyspnea and physical functioning following treatment with pembrolizumab plus maintenance olaparib compared to pembrolizumab plus placebo in participants with stage IV squamous non-small cell lung cancer (NSCLC) with stable disease (SD), partial response (PR), or complete response (CR) following induction treatment with pembrolizumab combined with carboplatin and a taxane (paclitaxel or nab-paclitaxel)

Main Objective: 1.To compare pembrolizumab plus maintenance olaparib with pembrolizumab plus placebo with respect to progression-free survival (PFS) assessed according to RECIST 1.1 by blinded independent central review (BICR) in participants with stage IV squamous non-small cell lung cancer (NSCLC) with stable disease (SD), partial response (PR), or complete response (CR) following induction treatment with pembrolizumab combined with carboplatin and a taxane (paclitaxel or nab paclitaxel)
2.To compare pembrolizumab plus maintenance olaparib with pembrolizumab plus placebo with respect to overall survival (OS) in participants with stage IV squamous non-small cell lung cancer (NSCLC) with stable disease (SD), partial response (PR), or complete response (CR) following induction treatment with pembrolizumab combined with carboplatin and a taxane (paclitaxel or nab paclitaxel)

Timepoint(s) of evaluation of this end point: 1.Up to ~3 years
2.Up to ~5 years

Secondary Outcome(s)

Secondary end point(s): 1.Number of participants with one or more adverse events (AEs)
2.Number of participants discontinuing study intervention due to adverse events (AEs)
3.Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status / Quality of Life (Items 29 & 30) Scale Score
4.Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ LC13) Cough (Item 1) Scale Score
5.Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ LC13) Chest Pain (Item 10) Scale Score
6.Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Dyspnea (Item 8) Scale Score
7.Change from Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Physical Functioning (Items 1 to 5) Scale Score
8.Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status / Quality of Life (Items 29 & 30) Scale Score
9.Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 1) Scale Score
10.Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Chest Pain (Item 10) Scale Score
11.Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Dyspnea (Item 8) Scale Score
12.Time to True Deterioration (TTD) in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Physical Functioning (Items 1 to 5) Scale Score

Timepoint(s) of evaluation of this end point: 1.Up to ~5 years
2.Up to ~5 years
3.Baseline (at randomization) and Week 18 post-randomization
4.Baseline (at randomization) and Week 18 post-randomization
5.Baseline (at randomization) and Week 18 post-randomization
6.Baseline (at randomization) and Week 18 post-randomization
7.Baseline (at randomization) and Week 18 post-randomization
8.Up to ~5 years
9.Up to ~5 years
10.Up to ~5 years
11.Up to ~5 years
12.Up to ~5 years

Secondary ID(s)

2018-004721-88-AT

MK-7339-008

Source(s) of Monetary Support

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Ethics review

Status: Approved
Approval date: 08/07/2019
Contact: