Pembrolizumab in Combination With Axitinib Versus Sunitinib Monotherapy in Participants With Renal Cell Carcinoma

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

16 Sep 2016 → 26 Dec 2025

Decision date (initial)

2023-12-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pfizer · Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-507294-18-00

EudraCT number

2016-000588-17

WHO UTN

U1111-1295-6836

ClinicalTrials.gov

NCT02853331

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Safety, Pharmacokinetic, Pharmacodynamic, Therapy, Efficacy, Pharmacogenetic

1. To evaluate and compare PFS per RECIST 1.1 as assessed by BICR in subjects treated with pembrolizumab plus axitinib versus sunitinib monotherapy.
2. To evaluate and compare OS in subjects treated with pembrolizumab plus axitinib versus sunitinib monotherapy.

Secondary objectives 5

1. To compare ORR and DCR per RECIST 1.1 as assessed by BICR in subjects treated with a combination of pembrolizumab plus axitinib versus sunitinib monotherapy. DOR will also be evaluated.
2. To evaluate PFS rate per RECIST 1.1 as assessed by BICR at 12, 18, and 24 months based on data adequacy; to evaluate OS rates at 12, 18, and 24 months based on data adequacy.
3. To evaluate and compare safety and tolerability profiles in subjects treated with pembrolizumab plus axitinib versus sunitinib monotherapy.
4. To compare time to deterioration (TTD) based on the Functional Assessment of Cancer Therapy Kidney Symptom Index—Disease-Related Symptoms (FKSI-DRS) scale in subjects treated with pembrolizumab plus axitinib versus sunitinib monotherapy.
5. To assess the longitudinal score changes from baseline to 42 weeks as measured by European Organization for the Research and Treatment of Cancer (EORTC) QLQ-C30 global health status/quality of life scale.

Conditions and MedDRA coding

Metastatic renal cell carcinoma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Has histologically confirmed diagnosis of renal cell carcinoma (RCC) with clear cell component with or without sarcomatoid features
2. Has locally advanced/metastatic disease (i.e., newly diagnosed Stage IV RCC per American Joint Committee on Cancer) or has recurrent disease
3. Has measurable disease per RECIST 1.1 as assessed by the investigator/site radiologist
4. Has received no prior systemic therapy for advanced RCC.
5. Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
6. Has Karnofsky performance status (KPS) ≥ 70% as assessed within 10 days prior to randomization.
7. If receiving bone resorptive therapy (including but not limited to bisphosphonate or receptor activator of nuclear factor-kappa B ligand [RANK-L] inhibitor) must have therapy initiated at least 2 weeks prior to randomization.
8. Demonstrates adequate organ function.
9. Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study drug.
10. Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study drug through 120 days after the last dose of study drug.

Exclusion criteria 27

1. 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 randomization.
2. Has had major surgery within 4 weeks, received radiation therapy within 2 weeks prior to randomization, or has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to prior treatment.
3. Has had prior treatment with any anti-programmed cell death (anti-PD-1), or programmed cell death ligand 1 (PD-L1), or PD-L2 agent or an antibody targeting any other immune-regulatory receptors or mechanisms.
4. Has received prior systemic anti-cancer therapy for RCC with vascular endothelial growth factor (VEGF)/VEGF receptors (VEGFR) or mechanistic target of rapamycin (mTOR) targeting agents.
5. Has a history of severe hypersensitivity reaction (e.g., generalized rash/erythema, hypotension, bronchospasm, angioedema or anaphylaxis) to axitinib or sunitinib.
6. Has a diagnosis of immunodeficiency OR is receiving a systemic steroid therapy exceeding physiologic corticosteroid dose or any other form of immunosuppressive therapy within 7 days prior to randomization, except in the case of central nervous system (CNS) metastases.
7. Has an active autoimmune disease requiring systemic treatment with in the past 2 years OR a documented history of clinically severe autoimmune disease. Note: Participants with vitiligo, Sjøgren's syndrome, Type 1 diabetes, resolved childhood asthma/atopy, hypothyroidism or adrenal or pituitary insufficiency who are stable on hormone replacement, are not excluded.
8. Has a known additional malignancy that has progressed or has required active treatment in the last 3 years. Note: Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ such as breast cancer in situ are acceptable if they have undergone potentially curative therapy.
9. Has known active CNS metastases and/or carcinomatous meningitis.
10. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
11. Has an active infection requiring systemic therapy.
12. Has a known history of Human Immunodeficiency Virus (HIV).
13. Has known active Hepatitis B or Hepatitis C infection.
14. Has received a live virus vaccine within 30 days of randomization.
15. Has a clinically significant gastrointestinal (GI) abnormality including: malabsorption, total gastric resection, or any condition that might affect the absorption of orally taken medication; active GI bleeding, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy; intraluminal metastatic lesion with suspected bleeding, inflammatory bowel disease, ulcerative colitis or other GI condition associated with increased risk of perforation.
16. Has QT interval corrected for heart rate (QTc) ≥480 msec.
17. Has a history of any of the following cardiovascular conditions within 12 months of randomization: myocardial infarction, unstable angina pectoris, cardiac angioplasty or stenting, coronary/peripheral artery bypass graft, class III or IV congestive heart failure per New York Heart Association, cerebrovascular accident or transient ischemic attack.
18. Has a history of deep vein thrombosis or pulmonary embolism within 6 months of screening.
19. Has poorly controlled hypertension defined as systolic blood pressure (SBP) ≥150 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg.
20. Has evidence of inadequate wound healing.
21. Has active bleeding disorder or other history of significant bleeding episodes within 30 days of randomization.
22. Has hemoptysis within 6 weeks prior to randomization.
23. Has current use (within 7 days of randomization) or anticipated need for treatment with drugs or foods that are known strong cytochrome P450 (CYP3A4/5) inhibitors.
24. Has current use (within 7 days of randomization) or anticipated need for treatment with drugs that are known strong CYP3A4/5 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort; or drugs that are known with proarrhythmic potential.
25. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
26. Has had a prior solid organ transplant.
27. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug.

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) as Assessed by Blinded Independent Central Imaging Review
2. Overall Survival (OS)

Secondary endpoints 13

1. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Imaging Review
2. Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Imaging Review
3. Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Imaging Review
4. Number of Participants Who Experienced an Adverse Event (AE)
5. Number of Participants Who Discontinued Study Drug Due to an AE
6. Progression Free Survival Rate (PFS Rate) at Month 12 in All Participants
7. Progression Free Survival Rate (PFS Rate) at Month 18 in All Participants
8. Progression Free Survival Rate (PFS Rate) at Month 24 in All Participants
9. Overall Survival (OS) Rate at Month 12 in All Participants
10. Overall Survival (OS) Rate at Month 18 in All Participants
11. Overall Survival (OS) Rate at Month 24 in All Participants
12. Time to True Deterioration (TTD) of the Functional Assessment of Cancer Therapy Kidney Symptom Index Disease-Related Symptoms (FKSI-DRS) Score
13. Least Squares (LS) Mean Change From Baseline to Week 54 in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (GHS) Scale Score

Investigational products

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

Test 2

Comparator 1

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

Karla Rodriguez

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Karla Rodriguez

Third parties 6

Locations

7 EU/EEA countries · 46 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 68 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications