A Study Evaluating the Effect of Pembrolizumab (MK-3475) in Participants With Renal Cell Cancer (MK-3475-031)

NCT02212730 | Terminated Phase 1 Results

• 4 other identifiers: 3475-0312014-002526-12MK-3475-031KEYNOTE-031
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will examine the effect of treatment with the neoadjuvant antibody pembrolizumab (MK-3475) on tumors of participants with renal cell cancer (RCC). The primary hypotheses are that pembrolizumab is well tolerated in participants undergoing RCC tumor resection; and that pembrolizumab will stimulate a 2-fold or greater increase in intratumoral lymphocytic infiltration in at least 30% of participants with RCC.

Conditions

Renal Cell Cancer

Outcome Measures

Primary Outcomes (5)

• Number of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen

  An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE during their regimen of neoadjuvant pembrolizumab was presented.

  Up to Week 16

• Number of Participants Who Discontinued Treatment Due to an Adverse Event

  An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study drug due to an adverse event is presented.

  Up to 56 weeks

• Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD3+ Lymphocytic Infiltration

  The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD3+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.

  Baseline and Week 7

• Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD8+ Lymphocytic Infiltration

  The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD8+ lymphocytic infiltration is presented. Evaluations were based on pathologist score.

  Baseline and Week 7

• Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral FoxP3+ Lymphocytic Infiltration

  The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral FoxP3+ (forkhead box protein P3 positive) lymphocytic infiltration is presented. Evaluations were based on pathologist score.

  Baseline and Week 7

Secondary Outcomes (5)

• Change From Baseline in Levels of Gene Expression of Immune Modulatory Receptors in Tumors of Participants Treated With Neoadjuvant Pembrolizumab

  Baseline and Week 7

• Change From Baseline in Number of T Cells in Tumors of Participants Treated With Neoadjuvant Pembrolizumab

  Baseline and Week 7

• Change From Baseline in Number of Activated T Cells in Peripheral Blood of Participants Treated With Neoadjuvant Pembrolizumab

  Baseline and Week 7

• Change From Baseline in Levels of Programmed Cell Death 1 Ligand 1 (PD-L1) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab

  Baseline and Week 7

• Change From Baseline in Levels of Programmed Cell Death 1 Ligand 2 (PD-L2) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab

  Baseline and Week 7

Study Arms (2)

Neoadjuvant Pembrolizumab + RCC Resection

EXPERIMENTAL

Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.

Drug: Pembrolizumab Pre-Resection; Procedure: Surgical Resection; Drug: Pembrolizumab Post-Resection

RCC Resection

EXPERIMENTAL

Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles). Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04.

Procedure: Surgical Resection; Drug: Pembrolizumab Post-Resection

Interventions

Pembrolizumab Pre-Resection DRUG

200 mg administered by IV, once every 3-week cycle for a maximum of 2 cycles

Also known as: KEYTRUDA®, MK-3475

Neoadjuvant Pembrolizumab + RCC Resection

Surgical Resection PROCEDURE

Standard of care surgical resection of RCC tumor

Neoadjuvant Pembrolizumab + RCC Resection; RCC Resection

Pembrolizumab Post-Resection DRUG

200 mg administered by IV, once every 3-week cycle for a maximum of 17 cycles

Also known as: KEYTRUDA®, MK-3475

Neoadjuvant Pembrolizumab + RCC Resection; RCC Resection

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a newly diagnosed RCC, with a primary tumor diameter of more than 4 cm (\>= T1b), not previously treated, and be a candidate for operative tumor resection
• Be willing and able to undergo pre-treatment baseline image-guided core biopsy of their primary RCC
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
• Demonstrate adequate organ function
• Female is not breast feeding, is postmenopausal or surgically sterile; demonstrates non-pregnant state, and agrees to use two acceptable methods of birth control throughout the trial, until 120 days after the last dose of treatment
• Male with female partner of childbearing potential agrees to use adequate method of contraception throughout study, until 120 days after last dose of treatment or last blood draw.

You may not qualify if:

• Is currently participating in, or has participated in a study with an investigational agent or device within 4 weeks prior to first dose of study therapy
• Has a diagnosis of immunosuppression or has received systemic steroid therapy, or any other form of immunosuppressive therapy within 4 weeks prior to first dose of study therapy
• Has had prior chemotherapy, targeted small molecule, or radiation therapy for treatment of RCC
• Has a known additional (other than RCC) malignancy that is progressing or requires active treatment
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has an active, or documented history of autoimmune disease, with the exceptions of vitiligo or resolved childhood asthma/atopy
• Has a history of (non-infectious) pneumonitis that required treatment with steroids or current pneumonitis.
• Has an active infection requiring systematic therapy
• Is receiving anticoagulant therapy, with the exception of low dosage aspirin
• Has severe cardiovascular disease or symptomatic ischemic heart disease
• Has hepatic decompensation
• Has uncontrolled thyroid dysfunction
• Has uncontrolled diabetes mellitus
• Has known psychiatric or substance abuse disorders
• Female is pregnant or breastfeeding

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2014
• First Posted: August 8, 2014
• Study Start: December 3, 2014
• Primary Completion: July 5, 2019
• Study Completion: July 5, 2019
• Last Updated: July 16, 2020
• Results First Posted: July 16, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will share