AO-176 in Multiple Solid Tumor Malignancies

Solid Tumor Clinical Trial

Official title:

A Phase 1/2 Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of AO-176

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03834948
• Other study ID #: AO-176-101
• Secondary ID: KEYNOTE-C49
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 4, 2019
• Est. completion date: February 15, 2023

Study information

• Verified date: August 2023
• Source: Arch Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: February 15, 2023
• Est. primary completion date: November 17, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key 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

Key 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

Related Conditions & MeSH terms

• Solid Tumor

Intervention

Drug:
• AO-176
Humanized monoclonal antibody (mAb) targeting CD47
• AO-176 + Paclitaxel
Humanized monoclonal antibody (mAb) targeting CD47 and paclitaxel
• AO-176 + Pembrolizumab
Humanized monoclonal antibody (mAb) targeting CD47 and pembrolizumab

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of Virginia	Charlottesville	Virginia
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	University of Southern California	Los Angeles	California
United States	Tennessee Oncology	Nashville	Tennessee
United States	Oklahoma University, Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Sidney Kimmel Cancer Center, Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Oregon Health Science University	Portland	Oregon
United States	University of California San Francisco	San Francisco	California
United States	Northwest Medical Specialties	Tacoma	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Arch Oncology	Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	AO-176 anti-tumor activity assessed by changes in response criteria	Evaluate objective response rate of AO-176 using RECIST v1.1 and iRECIST.	Up to 12 months
Secondary	AO-176 + paclitaxel anti-tumor activity assessed by changes in response criteria	Evaluate objective response rate of AO-176 in combination with paclitaxel using RECIST v1.1 and iRECIST.	Up to 12 months
Secondary	AO-176 + pembrolizumab anti-tumor activity assessed by changes in response criteria	Evaluate objective response rate of AO-176 in combination with pembrolizumab using RECIST v1.1 and iRECIST.	Up to 12 months