AO-176 in Multiple Solid Tumor Malignancies

NCT ID: NCT03834948

Last Updated: 2023-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-04
• Study Completion Date: 2023-02-15

Brief Summary

This is a first-in-human, Phase 1/2 multi-center, open-label, dose escalation and expansion study of AO-176 which will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and clinical effects of AO-176 in patients with advanced solid tumors.

Detailed Description

This is a first-in-human, Phase 1/2 multicenter, open-label, dose escalation and expansion study of AO-176 in patients with solid tumors. Part A of this study will examine escalating repeat doses of AO-176 monotherapy in patients with select advanced solid tumors, including epithelial ovarian carcinoma (EOC), which will include primary peritoneal and fallopian tube carcinoma; squamous cell carcinoma of the head and neck; endometrial carcinoma; castration resistant prostate cancer; non-small cell lung adenocarcinoma; papillary thyroid carcinoma; pleural or peritoneal malignant mesothelioma; and gastroesophageal adenocarcinoma, for which standard therapy proven to provide clinical benefit does not exist or is no longer effective.

Part B and Part C of this study will examine escalating repeat doses of AO-176 in combination with paclitaxel (Part B) or pembrolizumab (Part C) in platinum-resistant EOC, including primary peritoneal and fallopian tube carcinoma; endometrial carcinoma; and gastric adenocarcinoma/gastroesophageal adenocarcinoma.

The monotherapy and combination dose escalation portions of the study utilize a classic 3+3 design, with enrollment of 3 patients per cohort and expansion of the cohort in the event of a dose-limiting toxicity (DLT).

Once the maximum-tolerated dose (MTD)/recommended phase 2 dose (RP2D) has been established in dose escalation, tumor-specific dose expansion cohorts will be recruited to further assess safety and evaluate preliminary efficacy of AO-176 as monotherapy, in combination with paclitaxel, and in combination with pembrolizumab.

Conditions

Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AO-176 Dose Escalation

Each dose escalation cohort will initially recruit 3 patients to receive AO-176 in a standard 3+3 design; cohorts will be expanded in the event of a DLT.

Group Type: EXPERIMENTAL

AO-176

Intervention Type: DRUG

Humanized monoclonal antibody (mAb) targeting CD47

AO-176 Dose Expansion

Once the MTD/RP2D has been established, tumor-specific dose expansion cohorts will be recruited to further assess safety and evaluate preliminary efficacy of AO-176.

Group Type: EXPERIMENTAL

AO-176

Intervention Type: DRUG

Humanized monoclonal antibody (mAb) targeting CD47

AO-176 + Paclitaxel Dose Escalation

Each dose escalation cohort will initially recruit 3 patients to receive AO-176 and paclitaxel in a standard 3+3 design; cohorts will be expanded in the event of a DLT.

Group Type: EXPERIMENTAL

AO-176 + Paclitaxel

Intervention Type: DRUG

Humanized monoclonal antibody (mAb) targeting CD47 and paclitaxel

AO-176 + Paclitaxel Dose Expansion

Once the MTD/RP2D has been established, tumor-specific dose expansion cohorts will be recruited to further assess safety and evaluate preliminary efficacy of AO-176 + paclitaxel.

Group Type: EXPERIMENTAL

AO-176 + Paclitaxel

Intervention Type: DRUG

Humanized monoclonal antibody (mAb) targeting CD47 and paclitaxel

AO-176 + Pembrolizumab Dose Escalation

Each dose escalation cohort will initially recruit 3 patients to receive AO-176 and pembrolizumab in a standard 3+3 design; cohorts will be expanded in the event of a DLT.

Group Type: EXPERIMENTAL

AO-176 + Pembrolizumab

Intervention Type: DRUG

Humanized monoclonal antibody (mAb) targeting CD47 and pembrolizumab

AO-176 + Pembrolizumab Dose Expansion

Once the MTD/RP2D has been established, tumor-specific dose expansion cohorts will be recruited to further assess safety and evaluate preliminary efficacy of AO-176 + pembrolizumab.

Group Type: EXPERIMENTAL

AO-176 + Pembrolizumab

Intervention Type: DRUG

Humanized monoclonal antibody (mAb) targeting CD47 and pembrolizumab

Interventions

AO-176

Humanized monoclonal antibody (mAb) targeting CD47

Intervention Type: DRUG

AO-176 + Paclitaxel

Humanized monoclonal antibody (mAb) targeting CD47 and paclitaxel

Intervention Type: DRUG

AO-176 + Pembrolizumab

Humanized monoclonal antibody (mAb) targeting CD47 and pembrolizumab

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Select advanced solid tumor for which standard therapy proven to provide clinical benefit does not exist, or is no longer effective

Part A:

• Epithelial ovarian carcinoma (EOC)
• Endometrial carcinoma
• Castration resistant prostate cancer
• Non-small cell lung adenocarcinoma
• Papillary thyroid carcinoma
• Malignant mesothelioma (pleural or peritoneal)
• Gastroesophageal adenocarcinoma
• Squamous cell carcinoma of the head and neck

Part B and Part C:

• Platinum-resistant EOC (including fallopian tube or primary peritoneal cancer)
• Endometrial carcinoma
• Gastric adenocarcinoma/gastroesophageal adenocarcinoma

2. Measurable disease

3. ECOG status 0-1

4. Resolution of prior-therapy-related adverse effects

5. Minimum of 4 weeks or 5 half-lives since last dose of cancer therapy

Exclusion Criteria

1. Previous hypersensitivity reaction to treatment with another monoclonal antibody

2. Unresolved hypersensitivity to paclitaxel or any of its excipients (Part B only). Patients who have been desensitized may participate.

3. Part C Only

1. History of interstitial lung disease or a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.

2. History of immune mediated colitis, hepatitis, endocrinopathies, nephritis or significant immune mediated skin reactions such as toxic epidermal necrolitis or Stevens -Johnson Syndrome

3. History of any autoimmune disease which required systemic therapy* in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs) including but not limited to: i. Inflammatory bowel disease (including ulcerative colitis and Crohn's Disease) ii. Rheumatoid arthritis iii. Systemic progressive sclerosis (scleroderma) iv. Systemic lupus erythematosus v. Autoimmune vasculitis (e.g. Wegener's granulomatosis) *Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed)

4. Prior treatment with a checkpoint inhibitor (anti-PD-1, PD-L1, CTLA-4 etc.) within 4 weeks prior to the start of study drug

5. Prior treatment with a CD47-targeted therapy

6. Prior organ or stem cell transplant

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Arch Oncology

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Benajmin Oshrine, MD

Role: STUDY_DIRECTOR

Arch Oncology

Locations

University of Southern California

Los Angeles, California, United States

University of California San Francisco

San Francisco, California, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Oklahoma University, Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Oregon Health Science University

Portland, Oregon, United States

Sidney Kimmel Cancer Center, Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Tennessee Oncology

Nashville, Tennessee, United States

University of Virginia

Charlottesville, Virginia, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

Northwest Medical Specialties

Tacoma, Washington, United States

Countries

United States

References

Andrejeva G, Capoccia BJ, Hiebsch RR, Donio MJ, Darwech IM, Puro RJ, Pereira DS. Novel SIRPalpha Antibodies That Induce Single-Agent Phagocytosis of Tumor Cells while Preserving T Cells. J Immunol. 2021 Feb 15;206(4):712-721. doi: 10.4049/jimmunol.2001019. Epub 2021 Jan 11.

Reference Type: DERIVED

PMID: 33431660 (View on PubMed)

Other Identifiers

KEYNOTE-C49

Identifier Type: OTHER

Identifier Source: secondary_id

AO-176-101

Identifier Type: -

Identifier Source: org_study_id