| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic Squamous Non-small Cell Lung Cancer (NSCLC) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Stage IV lung cancer condition |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10029514 |
| E.1.2 | Term | Non-small cell lung cancer NOS |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
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)
|
|
| E.2.2 | Secondary objectives of the trial |
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)
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 ≥18 years of age on day of signing informed consent
- Male participants are eligible to participate if they agree to the following during the intervention period for at least 180 days after the
last dose of study intervention:
• Refrain from donating sperm
• 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
• Agree to use contraception, unless confirmed to be azoospermic (vasectomized or secondary to medical cause [Appendix 5]), as detailed
below:
• Agree to use male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a
woman of childbearing potential (WOCBP) who is not currently pregnant.
Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom
during each episode of penile-vaginal penetration.
- A female participant is eligible to participate if she is not pregnant (Appendix 5), not breastfeeding, and at least 1 of the following
conditions applies:
a. Not a woman of childbearing potential (WOCBP).
OR
b. 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 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. A WOCBP must have a negative highly sensitive urine
pregnancy test as required by local regulations) within 24 hours (72 hours for serum) before the first dose of study intervention.
- 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 as assessed at Pre randomization visit (most recent assessment within this visit).
- All AEs (with the exception of alopecia, Grade 2 fatigue, and Grade ≤2 endocrine-related AEs requiring treatment or hormone replacement. For
anemia and creatinine clearance, the guidelines provided in Table 3 may be followed) resolved to Grade ≤ 1 or baseline following Induction Phase
treatment.
- Have adequate organ function.
- Are not taking medications or vaccinations specifically prohibited
- 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. |
|
| E.4 | Principal 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
- Receiving either strong or moderate inducers or inhibitor of CYP3A4 that cannot be discontinued for the duration of the study
|
|
| E.5 End points |
| E.5.1 | 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)
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1.Up to ~3 years
2.Up to ~5 years
|
|
| E.5.2 | 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 |
|
| E.5.2.1 | 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
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 93 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Australia |
| Brazil |
| Canada |
| Colombia |
| Japan |
| Korea, Republic of |
| Mexico |
| Peru |
| Puerto Rico |
| Thailand |
| United States |
| Austria |
| France |
| Poland |
| Sweden |
| Netherlands |
| Romania |
| Spain |
| Switzerland |
| Czechia |
| Germany |
| Hungary |
| Turkey |
| Ukraine |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
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