AO-176 in Multiple Solid Tumor Malignancies | NCT03834948

NCT03834948

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
KEYNOTE-C49	Other Identifier	Merck Sharp & Dohme Corp.

Status Module

Name	Class
Merck Sharp & Dohme LLC	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
AO-176 Dose Escalation	Experimental	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
AO-176 Dose Expansion	Experimental	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
AO-176 + Paclitaxel Dose Escalation	Experimental	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
AO-176 + Paclitaxel Dose Expansion	Experimental	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
AO-176 + Pembrolizumab Dose Escalation	Experimental	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.

Name	Type	Description	Arm Group Labels	Other Names
AO-176	Drug	Humanized monoclonal antibody (mAb) targeting CD47	AO-176 Dose Escalation AO-176 Dose Expansion

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	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.	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.	Up to 12 months

Secondary Outcomes

Measure	Description	Time Frame
AO-176 anti-tumor activity assessed by changes in response criteria	Evaluate objective response rate of AO-176 using RECIST v1.1 and iRECIST.	Up to 12 months
AO-176 + paclitaxel anti-tumor activity assessed by changes in response criteria

Eligibility Module

Eligibility Criteria

Key Inclusion Criteria

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.
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)
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

Facility	Status	City	State	ZIP	Country	Contacts
University of Southern California		Los Angeles	California	90033	United States
University of California San Francisco