AO-176 in Multiple Solid Tumor Malignancies
- Conditions
- Solid Tumor
- Interventions
- Registration Number
- NCT03834948
- Lead Sponsor
- Arch Oncology
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 57
Not provided
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description AO-176 + Paclitaxel Dose Escalation AO-176 + Paclitaxel 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. AO-176 + Pembrolizumab Dose Escalation AO-176 + Pembrolizumab 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. AO-176 + Pembrolizumab Dose Expansion AO-176 + Pembrolizumab 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. AO-176 + Paclitaxel Dose Expansion AO-176 + Paclitaxel 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. AO-176 Dose Escalation AO-176 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. AO-176 Dose Expansion AO-176 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.
- Primary Outcome Measures
Name Time Method Safety of AO-176 assessed by adverse events and laboratory abnormalities Up to 12 months Evaluate the safety of AO-176 measured by the number adverse events, serious adverse events and lab abnormalities.
Safety of AO-176 and paclitaxel assessed by adverse events and laboratory abnormalities Up to 12 months Evaluate the safety of AO-176 in combination with paclitaxel measured by the number adverse events, serious adverse events and lab abnormalities.
Safety of AO-176 and pembrolizumab assessed by adverse events and laboratory abnormalities Up to 12 months Evaluate the safety of AO-176 in combination with pembrolizumab measured by the number adverse events, serious adverse events and lab abnormalities.
- Secondary Outcome Measures
Name Time Method AO-176 anti-tumor activity assessed by changes in response criteria Up to 12 months Evaluate objective response rate of AO-176 using RECIST v1.1 and iRECIST.
AO-176 + paclitaxel anti-tumor activity assessed by changes in response criteria Up to 12 months Evaluate objective response rate of AO-176 in combination with paclitaxel using RECIST v1.1 and iRECIST.
AO-176 + pembrolizumab anti-tumor activity assessed by changes in response criteria Up to 12 months Evaluate objective response rate of AO-176 in combination with pembrolizumab using RECIST v1.1 and iRECIST.
Trial Locations
- Locations (10)
Northwest Medical Specialties
🇺🇸Tacoma, Washington, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
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
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States