Study of AB598 Monotherapy and Combination Therapy in Participants With Advanced Cancers

Study Overview
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Brief Summary
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The primary purpose of this study is to assess the safety and tolerability of AB598 when taken alone, and in combination with zimberelimab and standard chemotherapy in participants with advanced malignancies.

Official Title
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A Phase 1/1b Study to Evaluate the Safety and Tolerability of AB598 Monotherapy and Combination Therapy in Participants With Advanced Malignancies

Conditions
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Advanced Cancer, Advanced Malignancies, Bladder Cancer, Cervical Cancer, Esophageal Cancer, Gastric Cancer, Gastroesophageal-junction Cancer (GEJ), Head and Neck Squamous Cell Carcinoma (HNSCC), Non-Small Cell Lung Cancer (NSCLC), Ovarian Cancer, Renal Cell Carcinoma (RCC), Triple Negative Breast Cancer (TNBC)

Intervention / Treatment
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* Drug: AB598
* Drug: Zimberelimab
* Drug: Carboplatin
* Drug: Pemetrexed
* Drug: Fluorouracil
* Drug: Leucovorin
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) guidance Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 Monotherapy-specific criteria for dose escalation cohorts: Participants may have pathologically confirmed NSCLC, gastric/GEJ, esophageal, HNSCC, bladder, RCC, TNBC, cervical, and ovarian cancers for which standard therapy has proven ineffective, intolerable, or considered inappropriate Disease-specific criteria for dose-expansion Cohort 1 (NSCLC): Histologically confirmed, documented diagnosis of locally advanced unresectable or metastatic non-squamous NSCLC Treatment-naive in the unresectable locally advanced or metastatic setting Cannot have progressed within 6 months of prior platinum-based chemotherapy Mixed small-cell lung cancer histology is not permitted Disease-specific criteria for dose expansion Cohort 2 (Gastric/GEJ): Histologically confirmed, documented diagnosis of human epidermal growth factor 2 (HER2)-negative locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma No prior systemic treatment for locally advanced unresectable or metastatic disease Cannot have progressed within 6 months of prior platinum-based chemotherapy Key Exclusion Criteria: Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of study Underlying medical conditions or AEs that, in the investigator's or sponsor's opinion, will make the administration of the study drugs hazardous Any active or documented history of autoimmune disease including but not limited to inflammatory bowel disease, celiac disease, Wegner syndrome, Hashimoto syndrome, systemic lupus erythematosus, scleroderma, sarcoidosis, or autoimmune hepatitis, within 3 years of the first dose of study treatment History of trauma or major surgery within 28 days prior to the first dose of study drug Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressant medication during study treatment with certain protocol specified exceptions Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Cohort 1<br>Participants will receive AB598 intravenous (IV) infusion once every 3 weeks | Drug: AB598<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Escalation Cohort 2<br>Participants will receive AB598 IV infusion once every 3 weeks | Drug: AB598<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Escalation Cohort 3<br>Participants will receive AB598 IV infusion once every 3 weeks | Drug: AB598<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Escalation Cohort 4<br>Participants will receive AB598 IV infusion once every 3 weeks | Drug: AB598<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Expansion Cohort 1 NSCLC<br>Participants will receive AB598 IV infusion in combination with zimberelimab and carboplatin/pemetrexed once every 3 weeks, for up to 2 years | Drug: AB598<br>* Administered as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered as specified in the treatment arm<br>* Other names: AB122;Drug: Carboplatin<br>* Administered as specified in the treatment arm<br>Drug: Pemetrexed<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Expansion Cohort 2 Gastric/GEJ Cancer<br>Participants will receive AB598 IV infusion in combination with zimberelimab once every 3 weeks, and FOLFOX (oxaliplatin, leucovorin, fluorouracil) every 2 weeks, for up to 2 years | Drug: AB598<br>* Administered as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered as specified in the treatment arm<br>* Other names: AB122;Drug: Fluorouracil<br>* Administered as specified in the treatment arm<br>Drug: Leucovorin<br>* Administered as specified in the treatment arm<br>Drug: Oxaliplatin<br>* Administered as specified in the treatment arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Up to 2 years | 
| Dose Escalation Cohorts: Number of Participants with Dose-Limiting Toxicities (DLTs) |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-Time Curve from Administration (0) to the Time That the Drug is No Longer Present in the Body (infinity) (AUC 0-inf) in Whole Blood and Plasma |  | Predose, Up to 4 hours postdose | 
| Maximum Concentration (Cmax) in Whole Blood and Plasma |  | Predose, Up to 4 hours postdose | 
| Time to Maximum Concentration (Tmax) in Whole Blood and Plasma |  | Predose, Up to 4 hours postdose | 
| Number of Participants Who Test Positive for Antidrug Antibodies (ADAs) to AB598 |  | Up to 2 years | 
| Objective Response Rate (ORR) |  | Up to 2 years | 
| Dose Expansion Cohorts: Duration of Response (DOR) |  | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AB598, AB122, Zimberelimab