Pembrolizumab (Anti-PD-1) and AMG386 (Angiopoietin-2 (Ang-2) in Patients With Advanced Solid Tumor

NCT03239145 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 17-217
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 2

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

Conditions

Advanced Solid Tumor

Keywords

Advanced Solid Tumor; Melanoma; Ovarian Cancer; Renal Cancer; Colorectal Cancer

Outcome Measures

Primary Outcomes (3)

• Number of Participants Experienced Dose Limit Toxicities (DLT)

  A standard 3+3 dose-escalation design was used during dose escalation period. DLT was defined in protocol section 5.5.

  3 weeks

• Maximum Tolerated Dose (MTD) of Trebananib

  MTD will be defined as the dose level at which fewer than one-third of participants experience a dose-limiting toxicity attributable to pembrolizumab and trebananib, as determined using a standard 3+3 dose-escalation design.

  3 weeks

• Grade 3 or Higher Toxicity Rate in Expansion Cohort

  The percentage of participants who experienced grade 3 or higher event based on the Common Toxicity Criteria for Adverse Events Version 4.0 (CTCAEv4).

  The median follow up time was 3.3 months (range: 0.6 to 25.3 months).

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Median follow-up was 29.3 months (range 0.9 - 42.0 months).

• Progression Free Survival at 6 Months (PFS6)

  6 months

• Overall Survival at 1 Year (OS1)

  1 year

• Median Time To Progression (TTP)

  ian follow-up was 29.3 months (range 0.9 - 42.0 months).

Study Arms (5)

[Dose Escalation Dose Level I] Pembrolizumab + Trebananib

EXPERIMENTAL

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

Drug: Pembrolizumab; Drug: Trebananib

[Dose Expansion] Pembrolizumab + Trebananib (Ovarian)

EXPERIMENTAL

Participants received pembrolizumab 200 mg administered intravenously every 3 weeks in combination with trebananib administered intravenously at 30 mg/kg weekly.

Drug: Pembrolizumab; Drug: Trebananib

[Dose Expansion] Pembrolizumab + Trebananib (Colorectal)

EXPERIMENTAL

Participants received pembrolizumab 200 mg administered intravenously every 3 weeks in combination with trebananib administered intravenously at 30 mg/kg weekly.

Drug: Pembrolizumab; Drug: Trebananib

[Dose Expansion] Pembrolizumab + Trebananib (Renal Cell Carcinoma)

EXPERIMENTAL

Participants received pembrolizumab 200 mg administered intravenously every 3 weeks in combination with trebananib administered intravenously at 30 mg/kg weekly.

Drug: Pembrolizumab; Drug: Trebananib

[Dose Escalation Dose Level II] Pembrolizumab + Trebananib

EXPERIMENTAL

Participants received pembrolizumab 200 mg administered intravenously every 3 weeks in combination with trebananib administered intravenously at 30 mg/kg weekly.

Drug: Pembrolizumab; Drug: Trebananib

Interventions

Pembrolizumab DRUG

Pembrolizumab is designed to augment the natural ability of the immune system to recognize and target cancer cells

Also known as: Keytruda

[Dose Escalation Dose Level II] Pembrolizumab + Trebananib; [Dose Escalation Dose Level I] Pembrolizumab + Trebananib; [Dose Expansion] Pembrolizumab + Trebananib (Colorectal); [Dose Expansion] Pembrolizumab + Trebananib (Ovarian); [Dose Expansion] Pembrolizumab + Trebananib (Renal Cell Carcinoma)

Trebananib DRUG

AMG386 is a drug that may kill tumor cells and blocks blood vessels that supply the tumor with nutrients and oxygen

Also known as: AMG 386

[Dose Escalation Dose Level II] Pembrolizumab + Trebananib; [Dose Escalation Dose Level I] Pembrolizumab + Trebananib; [Dose Expansion] Pembrolizumab + Trebananib (Colorectal); [Dose Expansion] Pembrolizumab + Trebananib (Ovarian); [Dose Expansion] Pembrolizumab + Trebananib (Renal Cell Carcinoma)

Eligibility Criteria

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

You may qualify if:

• 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 1.1.
• 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.
• Patients with melanoma should have unresectable or metastatic disease. Melanoma patients with BRAF V600E or V600K mutation-positive melanoma who have previously received a BRAF inhibitor with or without a MEK inhibitor) are eligible.
• In the dose expansion cohort patients should be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion (pre-treatment) and post-treatment biopsy. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1. Patients for whom newly-obtained samples cannot be provided (e.g., inaccessible, subject safety concern, or unwilling to undergo biopsy) may submit an archived specimen only upon agreement from the Sponsor. An on-treatment biopsy will be collected approximately halfway through the induction period, about 6 weeks from the start of study treatment (sometime between Cycle 2 Day 8 - Cycle 3 Day 1).
• Have a performance status of 0 or 1 on the ECOG Performance Scale (see Appendix A) up to 28 days before treatment initiation
• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed up to 28 days before treatment initiation.
• System Laboratory Value

You may not qualify if:

• 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.
• Ulcerated skin lesions
• Poorly-controlled hypertension as defined BP \> 150/100 mmHg, or SBP \> 180 mmHg when DBP \< 90 mmHg, on at least 2 repeated determinations on separate days within 3 months prior to study enrollment.
• History within 6 months prior to treatment of myocardial infarction, severe/unstable angina pectoris, CABG, NYHA class III or IV CHF, stroke or TIA.
• History within 3 months prior to treatment of Grade 3-4 GI bleeding/hemorrhage, treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolus, or other uncontrolled thromboembolic event.
• Patients who are less than 4 weeks post-op after major surgery.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Amgen: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Melanoma; Ovarian Neoplasms; Kidney Neoplasms; Colorectal Neoplasms

Interventions

pembrolizumab; trebananib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: F. Stephen Hodi, MD
• Organization: Dana-Farber Cancer Institute

Stephen_Hodi@dfci.harvard.edu

(617) 632-5053

Study Officials

• Stephen Hodi, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 1, 2017
• First Posted: August 3, 2017
• Study Start: May 1, 2018
• Primary Completion: December 13, 2024
• Study Completion: December 13, 2024
• Last Updated: March 12, 2026
• Results First Posted: March 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)