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AO-176 in Multiple Solid Tumor Malignancies

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ClinicalTrials.gov Identifier: NCT03834948
Recruitment Status : Recruiting
First Posted : February 8, 2019
Last Update Posted : July 8, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Arch Oncology

Study Description
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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.

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: AO-176 Drug: AO-176 + Paclitaxel Drug: AO-176 + Pembrolizumab Phase 1 Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 183 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Each dose escalation cohort will initially recruit 3 patients to receive AO-176 or AO-176 + paclitaxel or AO-176 + pembrolizumab in a standard 3+3 design; the cohort will be expanded in the event of a DLT.

Once the MTD/RP2D has been established for monotherapy, AO-176 + paclitaxel or AO-176 + pembrolizumab, tumor-specific dose expansion cohorts will be recruited to further assess safety and evaluate preliminary efficacy.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 4, 2019
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2023
Arms and Interventions
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Arm Intervention/treatment
Experimental: AO-176 Dose Escalation
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.
 Drug: AO-176
Humanized monoclonal antibody (mAb) targeting CD47
Experimental: AO-176 Dose Expansion
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.
 Drug: AO-176
Humanized monoclonal antibody (mAb) targeting CD47
Experimental: AO-176 + Paclitaxel Dose Escalation
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.
 Drug: AO-176 + Paclitaxel
Humanized monoclonal antibody (mAb) targeting CD47 and paclitaxel
Experimental: AO-176 + Paclitaxel Dose Expansion
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.
 Drug: AO-176 + Paclitaxel
Humanized monoclonal antibody (mAb) targeting CD47 and paclitaxel
Experimental: AO-176 + Pembrolizumab Dose Escalation
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.
 Drug: AO-176 + Pembrolizumab
Humanized monoclonal antibody (mAb) targeting CD47 and pembrolizumab
Experimental: AO-176 + Pembrolizumab Dose Expansion
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.
 Drug: AO-176 + Pembrolizumab
Humanized monoclonal antibody (mAb) targeting CD47 and pembrolizumab


Outcome Measures
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Primary Outcome Measures :
  1. Safety of AO-176 assessed by adverse events and laboratory abnormalities [ Time Frame: Up to 12 months ]
    Evaluate the safety of AO-176 measured by the number adverse events, serious adverse events and lab abnormalities.

  2. Safety of AO-176 and paclitaxel assessed by adverse events and laboratory abnormalities [ Time Frame: 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.

  3. Safety of AO-176 and pembrolizumab assessed by adverse events and laboratory abnormalities [ Time Frame: 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 :
  1. AO-176 anti-tumor activity assessed by changes in response criteria [ Time Frame: Up to 12 months ]
    Evaluate objective response rate of AO-176 using RECIST v1.1 and iRECIST.

  2. AO-176 + paclitaxel anti-tumor activity assessed by changes in response criteria [ Time Frame: Up to 12 months ]
    Evaluate objective response rate of AO-176 in combination with paclitaxel using RECIST v1.1 and iRECIST.

  3. AO-176 + pembrolizumab anti-tumor activity assessed by changes in response criteria [ Time Frame: Up to 12 months ]
    Evaluate objective response rate of AO-176 in combination with pembrolizumab using RECIST v1.1 and iRECIST.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03834948


Contacts
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Contact: Arch Medical Monitor 415-988-2241 AO-176-101-CT.gov@archoncology.com
Contact: Sergio Rodriguez srodriguez@archoncology.com

Locations
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United States, California
University of Southern California Recruiting
Los Angeles, California, United States, 90033
Contact: Xiomara Menendez, RN,BSN       menendez_x@med.usc.edu   
Contact: Lorraine Martinez       Lorraine.Martinez@med.usc.edu   
Principal Investigator: Anthony El-Khoueriy, MD         
University of California San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Claire Hooker    415-353-7084    Claire.Hooker@ucsf.edu   
Principal Investigator: Pamela Munster, MD         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215-5450
Contact: Christin Whalen, RN, BSN, OCN       christin_whalen@dfci.harvard.edu   
Principal Investigator: Joyce Liu, MD, MPH         
United States, Oregon
Oregon Health Science University Active, not recruiting
Portland, Oregon, United States, 97239
United States, Tennessee
Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact    615-339-4214    asksarah@sarahcannon.com   
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Anne Gabel    434-982-6657    Am7bd@hscmail.mcc.virginia.edu   
Principal Investigator: Linda Duska         
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Contact: Claudia Phillips, RN, BSN, OCN, CCRP       claudia.phillips@usoncology.com   
Principal Investigator: Alex Spira, MD         
Sponsors and Collaborators
Arch Oncology
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Naimish Pandya Arch Oncology
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Arch Oncology
ClinicalTrials.gov Identifier: NCT03834948    
Other Study ID Numbers: AO-176-101
KEYNOTE-C49 ( Other Identifier: Merck Sharp & Dohme Corp. )
First Posted: February 8, 2019    Key Record Dates
Last Update Posted: July 8, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Arch Oncology:
CD47
AO-176
Immunotherapy
Additional relevant MeSH terms:
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Paclitaxel
Pembrolizumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
 Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological