Phase Ib Study to Test the Safety and Potential Synergy of Pembrolizumab (Anti-PD-1) and AMG386 (Angiopoietin-2 (Ang-2) in Patients With Advanced Solid Tumor

Dana-Farber Cancer Institute2 sites in 1 country62 target enrollmentMay 1, 2018

ConditionsAdvanced Solid Tumor

InterventionsPembrolizumab Trebananib

DrugsPembrolizumab Trebananib

Overview

Phase: Phase 1
Intervention: Pembrolizumab
Conditions: Advanced Solid Tumor
Sponsor: Dana-Farber Cancer Institute
Enrollment: 62
Locations: 2
Primary Endpoint: Number of Participants Experienced Dose Limit Toxicities (DLT)
Status: Completed
Last Updated: last month

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This research study is studying an investigational combination of drugs as a possible treatment for advanced solid tumors: melanoma, ovarian, renal, or colorectal cancer.

The drugs involved in this study are:

Pembrolizumab
AMG386

Detailed Description

This research study is a Phase Ib clinical trial, which tests the safety of an investigational combination of drugs and also tries to define the appropriate dose of the investigational drugs to use for further studies. "Investigational" means that the drug is being studied. FDA (the U.S. Food and Drug Administration) has not approved of the combination of the study drugs pembrolizumab and AMG386 as a treatment for any disease. However, the FDA has approved pembrolizumab by itself for melanoma and non-small cell lung cancer. Pembrolizumab is a humanized monoclonal antibody, or specialized type of protein, produced in the laboratory for use in treating patients with the participant disease. Pembrolizumab is designed to augment the natural ability of the immune system to recognize and target cancer cells. AMG386 is a drug that may kill tumor cells and blocks blood vessels that supply the tumor with nutrients and oxygen. Drugs that block blood vessel formation are called "anti-angiogenic" therapies. AMG386 has been used and is currently being used in other clinical trials treating different types of cancer. Information from these other clinical trials suggests that this drug may help stop tumor growth. In this research study, the investigators are interested in looking at the combination of AMG386 with pembrolizumab because research done in the laboratory has suggested that the immunotherapy effect could be limited by the presence of tumor vessels in a process called angiogenesis. Adding AMG386 to pembrolizumab may help overcome this limitation and augment the effect of pembrolizumab. This combination of study drugs is being researched to: * Determine the safety and tolerability of pembrolizumab and AMG386 at different dose levels. * Determine the side effects of pembrolizumab and AMG386 when they are given in combination * Determine if pembrolizumab in combination with AMG386 is a possible treatment for cancer * Determine if pembrolizumab in combination with AMG386 changes immune cells in the blood or tumor

Registry

clinicaltrials.gov

Start Date

May 1, 2018

End Date

December 13, 2024

Last Updated

last month

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Dana-Farber Cancer Institute

Responsible Party

Principal Investigator

F. Stephen Hodi, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Inclusion Criteria

•Be willing and able to provide written informed consent for the trial.
•Be ≥ 18 years of age on day of signing informed consent.
•Have measurable disease based on RECIST 1.
•In dose escalation (Phase I), patients must have histologically or cytologically confirmed metastatic disease from any solid tumor that is incurable and fulfills one of the following criteria:
•Has demonstrated progression of disease following at least one line of effective systemic therapy. Prior treatment with anti-CTLA-4 antibody (including ipilimumab) is allowable OR
•For which effective therapy does not exist
•In dose expansion (part 2), patients must have histologically or cytologically confirmed unresectable or metastatic melanoma, renal cell carcinoma, ovarian cancer, or colorectal cancer.
•Renal cell patients must have had at least one prior VEGF TKI.
•Ovarian cancer patients must be resistant to platinum therapy (i.e. within 6 months of last platinum therapy).
•Patients with colorectal cancer should have progressed on at least one fluorouracil plus irinotecan or oxaliplatin containing regimen.

Exclusion Criteria

•Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
•Has a diagnosis of immunodeficiency including subjects infected with Human Immunodeficiency Virus (HIV).
•Is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
•Has a known history of active TB (Bacillus Tuberculosis).
•Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
•Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
•Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
•If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
•Has a known additional malignancy that is progressing or requires active treatment. -Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
•Lesions suspected to be at higher-risk for bleeding such as bowel involvement with tumor that invades into the bowel wall or involves the intraluminal component of bowel by imaging or direct visualization or central pulmonary lesions.

Arms & Interventions

[Dose Escalation Dose Level I] Pembrolizumab + Trebananib

Participants received pembrolizumab 200 mg administered intravenously every 3 weeks in combination with trebananib administered intravenously at 15 mg/kg weekly.

Intervention: Pembrolizumab

[Dose Escalation Dose Level I] Pembrolizumab + Trebananib

Participants received pembrolizumab 200 mg administered intravenously every 3 weeks in combination with trebananib administered intravenously at 15 mg/kg weekly.

Intervention: Trebananib