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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
57
Humanized monoclonal antibody (mAb) targeting CD47
Humanized monoclonal antibody (mAb) targeting CD47 and paclitaxel
Humanized monoclonal antibody (mAb) targeting CD47 and pembrolizumab
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
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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 12 months
AO-176 anti-tumor activity assessed by changes in response criteria
Evaluate objective response rate of AO-176 using RECIST v1.1 and iRECIST.
Time frame: Up to 12 months
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.
Time frame: Up to 12 months
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.
Time frame: Up to 12 months
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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