A Phase 1b Study of Demcizumab Plus Pembrolizumab in Locally Advanced or Metastatic Solid Tumors

• ClinicalTrials.gov Identifier: NCT02722954
• Recruitment Status: Completed
• First Posted: March 30, 2016
• Last Update Posted: August 11, 2020
• Sponsor: OncoMed Pharmaceuticals, Inc.
• Collaborator: Celgene Corporation
• Information provided by (Responsible Party): Mereo BioPharma ( OncoMed Pharmaceuticals, Inc. )

Study Description

Brief Summary:

The purpose of this study is to test the efficacy and safety of an experimental drug, demcizumab, when given in combination with pembrolizumab. Demcizumab is a humanized monoclonal antibody and was developed to target cancer stem cells. Demcizumab may block the growth of cancer stem cells, the remaining cancer cells, and it may also impair the productive growth of new blood vessels, which tumors need to grow and spread.

This study is sponsored by OncoMed Pharmaceuticals, which is referred to as OncoMed or the Sponsor in this consent form.

Condition or disease	Intervention/treatment	Phase
Locally Advanced or Metastatic Solid Tumors	Drug: Demcizumab; Drug: Pembrolizumab	Phase 1

Detailed Description:

This is an open-label, Phase 1b dose escalation and expansion study of demcizumab plus pembrolizumab designed to evaluate the safety, efficacy and pharmacokinetics of demcizumab in combination with pembrolizumab in patients with advanced or metastatic solid tumors. This study consists of a screening period, a treatment period and a post-treatment follow up period in which patients will be followed for survival for approximately 12 months. Patients will be enrolled in two stages: a dose-escalation stage and an expansion phase.

Approximately 42 patients will be enrolled in this study at approximately 10 study centers in the United States (U.S) and Europe.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b, Open-Label, Dose Escalation and Expansion Study of Demcizumab Plus Pembrolizumab in Patients With Locally Advanced or Metastatic Solid Tumors
• Study Start Date: January 2016
• Actual Primary Completion Date: May 10, 2017
• Actual Study Completion Date: May 19, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Demcizumab and Pembrolizumab; Demcizumab will be administered prior to pembrolizumab	Drug: Demcizumab; Drug: Demcizumab at starting dose of 2.5mg/kg administered intravenously (IV).; Other Name: OMP-21M18; Drug: Pembrolizumab; Drug: Pembrolizumab administered 2mg/kg IV every 3 weeks

Outcome Measures

Primary Outcome Measures :

1. Dose limiting toxicities (DLT) of demcizumab given in combination with pembrolizumab [ Time Frame: Subjects will be treated and observed for DLT through the end of the first cycle (Days 1-22) ]
   The maximum tolerated dose (MTD) or maximum administered dose (MAD) will be determined in patients treated with demcizumab in combination with pembrolizumab

Secondary Outcome Measures :

1. Pharmacokinetics (PK) of demcizumab and pembrolizumab [ Time Frame: Plasma sample for Pharmacokinetics (PK) analysis to be obtained on Days 1, 22, 43 then at every other cycle (each cycle is 21 days) until 12 weeks post treatment termination, an average of 1 year ]
   peak plasma concentration

Eligibility Criteria

• Ages Eligible for Study: 21 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1
2. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue, either fresh core-needle-biopsied or archived
3. Age >21 years
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
5. Adequate organ and marrow function
6. For women of childbearing potential and men with partners of childbearing potential, agreement (by patient and/or partner) to use two effective forms of contraception from study entry through at least 6 months after the termination visit.
7. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. Treatment with any anti-cancer therapy, including radiotherapy, chemotherapy, biologic therapy, or herbal therapy within 3 weeks or 5 half-lives (for systemic agents) whichever is shorter
2. Receiving any other investigational agents or any other anti-cancer therapy
3. Active infections requiring antibiotics
4. Patients with brain metastases (treated or untreated) leptomeningeal disease, uncontrolled seizure disorder, or active neurologic disease
5. History of interstitial lung disease or active, non-infectious pneumonitis that required oral or intravenous corticosteroids
6. Prior radiation to the chest wall or mediastinum if the radiation field involves the heart
7. Significant intercurrent illness that will limit the patient's ability to participate in the study or may result in their death over the next 18 months
8. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment, or anticipation of need for major surgical procedure during the course of the study
9. Pregnant or nursing women
10. New York Heart Association Classification II, III, or IV
11. Acute prior study treatment related toxicity (except alopecia) that has not resolved to Grade < or = to 1 unless it has been deemed stable by the investigator
12. Inability to comply with study and follow up procedure

Contacts and Locations

Locations

United States, Colorado

Rocky Mountain Cancer Center

Denver, Colorado, United States, 80218

United States, Michigan

University of Michigan Health System

Ann Arbor, Michigan, United States, 48109-5848

United States, New York

Columbia University Medical Center

New York, New York, United States, 10032

United States, Tennessee

Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

United States, Texas

The START Center for Cancer Care

San Antonio, Texas, United States, 78229

United Kingdom

The Royal Marsden NHS Foundation Trust

Sutton, Surrey, United Kingdom, SM2 5PT

Sponsors and Collaborators

OncoMed Pharmaceuticals, Inc.

Celgene Corporation

More Information

• Responsible Party: OncoMed Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02722954
• Other Study ID Numbers: M18-008
• First Posted: March 30, 2016
• Last Update Posted: August 11, 2020
• Last Verified: August 2020

Keywords provided by Mereo BioPharma ( OncoMed Pharmaceuticals, Inc. ):

malignancy; metastatic; Demcizumab; Pembrolizumab; Phase 1b

Additional relevant MeSH terms:

Neoplasms; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents