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
Brief SummaryThis 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 DescriptionThis 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 of this study will examine escalating repeat doses of AO-176 in combination with paclitaxel 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 and in combination with paclitaxel.
Inclusion and Exclusion Criteria
- Key Inclusion Criteria
- 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: - Platinum-resistant EOC (including fallopian tube or primary peritoneal cancer) - Endometrial carcinoma - Gastric adenocarcinoma/gastroesophageal adenocarcinoma
- Measurable disease
- ECOG status 0-1
- Resolution of prior-therapy-related adverse effects
- Minimum of 3 weeks or 5 half-lives since last dose of cancer therapy Key Exclusion Criteria:
- 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.
- 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
Please contact the trial administrator to learn more about where you can participate in this trial. Please use the contact form on the right side.