Clinical Trials /

AO-176 in Multiple Solid Tumor Malignancies

NCT03834948

Description:

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.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Endometrial Carcinoma
  • Esophageal Adenocarcinoma
  • Fallopian Tube Carcinoma
  • Gastric Adenocarcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Lung Adenocarcinoma
  • Malignant Mesothelioma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
  • Prostate Carcinoma
  • Thyroid Gland Papillary Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: AO-176 in Multiple Solid Tumor Malignancies
  • 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 IDs

  • ORG STUDY ID: AO-176-101
  • NCT ID: NCT03834948

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
AO-176AO-176 Dose Escalation
AO-176 + PaclitaxelAO-176 + Paclitaxel Dose Escalation

Purpose

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 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.
    

Trial Arms

NameTypeDescriptionInterventions
AO-176 Dose EscalationExperimentalEach 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
AO-176 Dose ExpansionExperimentalOnce 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.
  • AO-176
AO-176 + Paclitaxel Dose EscalationExperimentalEach 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 + Paclitaxel
AO-176 + Paclitaxel Dose ExpansionExperimentalOnce 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 + Paclitaxel

Eligibility Criteria

        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:

               -  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 3 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. Prior treatment with a checkpoint inhibitor (anti-PD-1, PD-L1, CTLA-4 etc.) within 4
             weeks prior to the start of study drug

          4. Prior treatment with a CD47-targeted therapy

          5. Prior organ or stem cell transplant
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety of AO-176 assessed by adverse events and laboratory abnormalities
Time Frame:Up to 12 months
Safety Issue:
Description:Evaluate the safety of AO-176 measured by the number adverse events, serious adverse events and lab abnormalities.

Secondary Outcome Measures

Measure:AO-176 Anti-Tumor Activity assessed by changes in response criteria
Time Frame:Up to 12 months
Safety Issue:
Description:Evaluate objective response rate of AO-176 using RECIST v1.1 and iRECIST.
Measure:AO-176 + Paclitaxel Anti-Tumor Activity assessed by changes in response criteria
Time Frame:Up to 12 months
Safety Issue:
Description:Evaluate objective response rate of AO-176 in combination with paclitaxel using RECIST v1.1 and iRECIST.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Arch Oncology

Trial Keywords

  • CD47
  • AO-176
  • Immunotherapy

Last Updated

September 17, 2020