AO-176 in Multiple Solid Tumor Malignancies

NCT03834948 | Completed Phase 1 FDA Drug

• 2 other identifiers: AO-176-101KEYNOTE-C49
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 10

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.

Conditions

Solid Tumor

Keywords

CD47; AO-176; Immunotherapy

Outcome Measures

Primary Outcomes (3)

• Safety of AO-176 assessed by adverse events and laboratory abnormalities

  Evaluate the safety of AO-176 measured by the number adverse events, serious adverse events and lab abnormalities.

  Up to 12 months

• Safety of AO-176 and paclitaxel assessed by adverse events and laboratory abnormalities

  Evaluate the safety of AO-176 in combination with paclitaxel measured by the number adverse events, serious adverse events and lab abnormalities.

  Up to 12 months

• Safety of AO-176 and pembrolizumab assessed by adverse events and laboratory abnormalities

  Evaluate the safety of AO-176 in combination with pembrolizumab measured by the number adverse events, serious adverse events and lab abnormalities.

  Up to 12 months

Secondary Outcomes (3)

• AO-176 anti-tumor activity assessed by changes in response criteria

  Up to 12 months

• AO-176 + paclitaxel anti-tumor activity assessed by changes in response criteria

  Up to 12 months

• AO-176 + pembrolizumab anti-tumor activity assessed by changes in response criteria

  Up to 12 months

Study Arms (6)

AO-176 Dose Escalation

EXPERIMENTAL

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.

Drug: AO-176

AO-176 Dose Expansion

EXPERIMENTAL

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.

Drug: AO-176

AO-176 + Paclitaxel Dose Escalation

EXPERIMENTAL

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.

Drug: AO-176 + Paclitaxel

AO-176 + Paclitaxel Dose Expansion

EXPERIMENTAL

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.

Drug: AO-176 + Paclitaxel

AO-176 + Pembrolizumab Dose Escalation

EXPERIMENTAL

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.

Drug: AO-176 + Pembrolizumab

AO-176 + Pembrolizumab Dose Expansion

EXPERIMENTAL

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.

Drug: AO-176 + Pembrolizumab

Interventions

AO-176 DRUG

Humanized monoclonal antibody (mAb) targeting CD47

AO-176 Dose Escalation; AO-176 Dose Expansion

AO-176 + Paclitaxel DRUG

Humanized monoclonal antibody (mAb) targeting CD47 and paclitaxel

AO-176 + Paclitaxel Dose Escalation; AO-176 + Paclitaxel Dose Expansion

AO-176 + Pembrolizumab DRUG

Humanized monoclonal antibody (mAb) targeting CD47 and pembrolizumab

AO-176 + Pembrolizumab Dose Escalation; AO-176 + Pembrolizumab Dose Expansion

Eligibility Criteria

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

You may qualify if:

• 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
• Measurable disease

You may not qualify if:

• Previous hypersensitivity reaction to treatment with another monoclonal antibody
• Unresolved hypersensitivity to paclitaxel or any of its excipients (Part B only). Patients who have been desensitized may participate.
• Part C Only
• History of interstitial lung disease or a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• History of immune mediated colitis, hepatitis, endocrinopathies, nephritis or significant immune mediated skin reactions such as toxic epidermal necrolitis or Stevens -Johnson Syndrome
• 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)
• Prior treatment with a checkpoint inhibitor (anti-PD-1, PD-L1, CTLA-4 etc.) within 4 weeks prior to the start of study drug
• Prior treatment with a CD47-targeted therapy
• Prior organ or stem cell transplant

Sponsors & Collaborators

• Arch Oncology: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (10)

University of Southern California

Los Angeles, California, 90033, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215-5450, United States

Location

Oklahoma University, Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health Science University

Portland, Oregon, 97239, United States

Location

Sidney Kimmel Cancer Center, Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

Related Publications (1)

• 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.

  PMID: 33431660 DERIVED

MeSH Terms

Interventions

Paclitaxel; pembrolizumab

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Benajmin Oshrine, MD

  Arch Oncology

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Each dose escalation cohort will initially recruit 3 patients to receive AO-176 or AO-176 + paclitaxel or AO-176 + pembrolizumab in a standard 3+3 design; the cohort will be expanded in the event of a DLT. Once the MTD/RP2D has been established for monotherapy, AO-176 + paclitaxel or AO-176 + pembrolizumab, tumor-specific dose expansion cohorts will be recruited to further assess safety and evaluate preliminary efficacy.

Study Record Dates

• First Submitted: February 4, 2019
• First Posted: February 8, 2019
• Study Start: February 4, 2019
• Primary Completion: November 17, 2022
• Study Completion: February 15, 2023
• Last Updated: August 22, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)