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

Merck Sharp & Dohme (MSD)

Status and phase: Terminated; Phase 1

Conditions: Renal Cell Cancer

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02212730

2014-002526-12 (EudraCT Number)

3475-031

MK-3475-031 (Other Identifier)

KEYNOTE-031 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 10 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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
• Is expecting to conceive children within the projected maximum duration of the trial, extending through 120 days after the last dose of treatment or the last blood draw
• Has received prior therapy with any antibody or drug (including ipilimumab) specifically targeting T-cell co-stimulation or checkpoint pathway
• Has a known history of human immunodeficiency virus (HIV)
• Has known active hepatitis B or C
• Has received a live vaccine within 30 days prior to screening

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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10 participants in 2 patient groups

Neoadjuvant Pembrolizumab + RCC Resection

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab Post-Resection

Drug: Pembrolizumab Pre-Resection

Procedure: Surgical Resection

RCC Resection

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab Post-Resection

Procedure: Surgical Resection