| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| First-line treatment of metastatic programmed cell death ligand 1 expressing (tumor proportion score ≥50%) non-small cell lung cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
| Previously untreated metastatic non-small cell lung cancer with tumors expressing PD-L1 ≥ 50% |
|
| 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 in combination with sacituzumab govitecan with pembrolizumab alone with respect to progression-free survival per RECIST 1.1 as assessed by blinded independent central review
2. To compare pembrolizumab in combination with sacituzumab govitecan with pembrolizumab alone with respect to overall survival |
|
| E.2.2 | Secondary objectives of the trial |
1. To compare pembrolizumab in combination with sacituzumab govitecan with pembrolizumab alone with respect to objective response rate per RECIST 1.1 as assessed by blinded independent central review
2. To evaluate duration of response per RECIST 1.1 by blinded independent central review for pembrolizumab in combination with sacituzumab govitecan and pembrolizumab alone
3. To evaluate the mean change from baseline (at randomization) in global health status/quality of life, physical functioning, role functioning, dyspnea, cough, and chest pain for pembrolizumab in combination with sacituzumab govitecan and pembrolizumab alone
4. To evaluate the time to deterioration in global health status/quality of life, physical functioning, role functioning, dyspnea, cough, and chest pain for pembrolizumab in combination with sacituzumab govitecan and pembrolizumab alone
5. To evaluate the safety and tolerability for pembrolizumab in combination with sacituzumab govitecan and pembrolizumab alone |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Has a histologically or cytologically confirmed diagnosis of NSCLC (Stage IV: M1a, M1b, M1c, AJCC Staging Manual, version 8).
2. Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology.
3. Has confirmation that EGFR-, ALK-, or ROS-1-directed therapy is not indicated as primary therapy (documentation of the absence of tumor-activating EGFR mutations [eg, DEL19 or L858R], AND absence of ALK and ROS-1 gene rearrangements).
4. Has provided tumor tissue that demonstrates PD-L1 expression in ≥50% of tumor cells (TPS ≥50%) as assessed by IHC at a central laboratory.
5. Is male or female, ≥18 years of age at the time of providing informed consent.
6. Has a life expectancy of at least 3 months.
7. If male, agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is as follows:
- sacituzumab govitecan: 95 days
- pembrolizumab: no requirement
• Refrains from donating sperm
PLUS either:
• Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent
OR
• Uses contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview) as detailed below:
- Uses 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. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
8. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies:
• Not a WOCBP
OR
• A WOCBP and:
- Uses 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 the time needed to eliminate each study intervention 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 length of time required to continue contraception for each study intervention is as follows:
o sacituzumab govitecan: 180 days
o pembrolizumab: 120 days
The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.
- Has a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
- Abstains from breastfeeding during the study intervention period and for at least 120 days after study intervention.
- Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a woman with an early undetected pregnancy.
9. The participant (or legally acceptable representative) has provided documented informed consent/assent for the study.
10. Has an ECOG Performance Status of 0 to 1 within 7 days before randomization.
11. Has adequate organ function as defined in the protocol. Specimens must be collected within 10 days before the start of study intervention. |
|
| E.4 | Principal exclusion criteria |
1. Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years.
2. Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC.
3. Has previously received treatment with any of the following:
• Topoisomerase 1 inhibitors. Any agent including an ADC containing a chemotherapeutic agent targeting topoisomerase 1.
• Trop-2-targeted therapy.
4. 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 coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137). Prior (neo)adjuvant therapy with PD-(L)1 agent is not allowed.
5. Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicities requiring corticosteroids.
6. Has received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study intervention.
7. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
8. Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration.
9. Cardiac disease
• Myocardial infarction or unstable angina pectoris within 6 months of enrollment.
• History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation. Participants who are stable on pacemaker only (without need for antiarrhythmic medication) can be included.
• NYHA Class III or greater congestive heart failure or left ventricular ejection fraction of <40%.
10. Has active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or GI perforation within 6 months of enrollment.
11. Has 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 medication.
12. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during study screening, are clinically stable and have not required steroid treatment for at least 14 days before the first dose of study intervention.
13. Has severe hypersensitivity (≥Grade 3) to pembrolizumab or sacituzumab govitecan and/or any of their excipients.
14. Has active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid).
15. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
16. Has active infection requiring systemic therapy.
17. Has history of HIV infection. HIV testing is not required unless mandated by local health authority.
18. History of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as detectable HCV RNA [qualitative]) infection.
19. Has history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
20. Has known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study.
21. Participants who have not adequately recovered from major surgery or have ongoing surgical complications.
22. History of allogenic tissue/solid organ transplant. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
1. Progression-Free Survival (PFS)
2. Overall Survival (OS) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 34 months
2. Up to approximately 48 months |
|
| E.5.2 | Secondary end point(s) |
1. Objective Response (OR)
2. Duration of Response (DOR)
3. Change from Baseline in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30)
4. Change from Baseline in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30
5. Change from Baseline in Role Functioning (Items 6-7) Combined Score on the EORTC QLQ-C30
6. Change from Baseline in Dyspnea Score (Item 8) on the EORTC QLQ-C30
7. Change from Baseline in Cough Score (Item 31) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Lung Cancer 13 (EORTC QLQ-LC13)
8. Change from Baseline in Chest Pain Score (Item 40) on the EORTC QLQ-LC13
9. Time to Deterioration (TTD) in the Global Health Status/Quality of Life (Items 29 and 30) Combined Score on the EORTC QLQ-C30
10. TTD in Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30
11. TTD in Role Functioning (Items 6-7) Combined Score on the EORTC QLQ-C30
12. TTD in Dyspnea Score (Item 8) on the EORTC QLQ-C30
13. TTD in Cough Score (Item 31) on the EORTC QLQ-LC13
14. TTD in in Chest Pain Score (Item 40) on the EORTC QLQ-LC13
15. Number of Participants Who Experience an Adverse Event (AE)
16. Number of Participants Who Discontinue Study Treatment Due to an AE
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 34 months
2. Up to approximately 48 months
3. Baseline and up to approximately 48 months
4. Baseline and up to approximately 48 months
5. Baseline and up to approximately 48 months
6. Baseline and up to approximately 48 months
7. Baseline and up to approximately 48 months
8. Baseline and up to approximately 48 months
9. Up to approximately 48 months
10. Up to approximately 48 months
11. Up to approximately 48 months
12. Up to approximately 48 months
13. Up to approximately 48 months
14. Up to approximately 48 months
15. Up to approximately 48 months
16. Up to approximately 48 months |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| 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 | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| 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 | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 39 |
| 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 |
| Australia |
| Brazil |
| Canada |
| Chile |
| China |
| Israel |
| Japan |
| Korea, Republic of |
| Malaysia |
| Mexico |
| Peru |
| Philippines |
| South Africa |
| Taiwan |
| Thailand |
| United States |
| Estonia |
| France |
| Latvia |
| Lithuania |
| Poland |
| Romania |
| Germany |
| Greece |
| Italy |
| Turkey |
| United Kingdom |
|
| 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 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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