A Study to Evaluate AB308 in Combination With AB122 in Participants With Advanced Malignancies

Study Overview
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Brief Summary
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This is a Phase 1/1b, multicenter, open-label, dose-escalation, and dose-expansion study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical activity of AB308 in combination with zimberelimab (AB122) in participants with advanced malignancies.

Official Title
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A Phase 1/1b Study to Evaluate the Safety and Tolerability of AB308 in Combination With AB122 in Participants With Advanced Malignancies

Conditions
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Advanced Solid Tumor, NSCLC, Melanoma, Cervical Cancer, Multiple Myeloma, Lymphoma, Non-Hodgkin, DLBCL, Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, Esophageal Cancer

Intervention / Treatment
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* Drug: AB308
* Drug: Zimberelimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Male or female participants ≥ 18 years of age (or age ≥ regionally approved age of consent for participation in investigational clinical studies) at the time of signing the informed consent. Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 Adequate organ and marrow function Exclusion Criteria: History of trauma or major surgery within 28 days prior to the first dose of study treatment. Prior treatment with an anti-TIGIT antibody. Any active or prior autoimmune disease that required treatment within 3 years of the first dose of study treatment. Prior chemotherapy, targeted small-molecule therapy, immunotherapy, or biologic agents, or use of other investigational drugs within 28 days before first dose of study treatment. Discontinued prior immunotherapy for immune related adverse events with a high severity. 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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Q3W Cohorts<br>Escalating doses of AB308 in combination with zimberelimab (360 mg) will be given every 3 weeks in participants with advanced malignancies. | Drug: AB308<br>* Administered intravenously (IV) as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered IV as specified in the treatment arm<br>* Other names: AB122;|
| Experimental: Dose Escalation Q4W Cohorts<br>Escalating doses of AB308 in combination with zimberelimab (480 mg) will be given every 4 weeks in participants with advanced malignancies. | Drug: AB308<br>* Administered intravenously (IV) as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered IV as specified in the treatment arm<br>* Other names: AB122;|
| Experimental: Dose Escalation Q6W Cohort<br>Selected dose of AB308 in combination with zimberelimab will be given every 6 weeks in participants with advanced malignancies. | Drug: AB308<br>* Administered intravenously (IV) as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered IV as specified in the treatment arm<br>* Other names: AB122;|
| Experimental: Dose Expansion Cohort 1<br>AB308 will be given in combination with zimberelimab at 360 mg or 480 mg Q3W or Q4W, respectively, in participants with in participants with locally advanced or metastatic NSCLC. | Drug: AB308<br>* Administered intravenously (IV) as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered IV as specified in the treatment arm<br>* Other names: AB122;|
| Experimental: Dose Expansion Cohort 2<br>AB308 will be given in combination with zimberelimab at 360 mg or 480 mg Q3W or Q4W, respectively, in participants with melanoma. | Drug: AB308<br>* Administered intravenously (IV) as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered IV as specified in the treatment arm<br>* Other names: AB122;|
| Experimental: Dose Expansion Cohort 3<br>AB308 will be given in combination with zimberelimab at 360 mg or 480 mg Q3W or Q4W, respectively, in participants with metastatic gastric, or gastroesophageal junction, or esophageal cancer. | Drug: AB308<br>* Administered intravenously (IV) as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered IV as specified in the treatment arm<br>* Other names: AB122;|
| Experimental: Dose Expansion Cohort 4<br>AB308 will be given in combination with zimberelimab at 360 mg or 480 mg Q3W or Q4W, respectively, in participants with cervical cancer. | Drug: AB308<br>* Administered intravenously (IV) as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered IV as specified in the treatment arm<br>* Other names: AB122;|
| Experimental: Dose Expansion Cohort 5<br>AB308 will be given in combination with zimberelimab at 360 mg or 480 mg Q3W or Q4W, respectively, in participants with hematological malignancies. | Drug: AB308<br>* Administered intravenously (IV) as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered IV as specified in the treatment arm<br>* Other names: AB122;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with Adverse Events |  | From first study treatment administration until up to 90 days after the last dose (Approximately 1 year) | 
| Percentage of participants who experience a Dose Limiting Toxicity |  | From first study treatment administration through Day 21 (Q3W arm) or Day 28 (Q4W arm) or Day 42 (Q6W arm) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum concentration of AB308 |  | Recorded at baseline (day 1 of cycle 1), during each of the first 5 cycles (each cycle is 21 days or 28 days or 42 days) and up to the first 16 cycles of treatment (up to 22 months), and 30 and 90 days post last dose (up to approximately 25 months) | 
| Serum concentration of zimberelimab |  | Recorded at baseline (day 1 of cycle 1), during each of the first 5 cycles (each cycle is 21 days or 28 days or 42 days) and up to the first 16 cycles of treatment (up to 22 months), and 30 and 90 days post last dose (up to approximately 25 months) | 
| Percentage of participants with anti-drug antibodies to AB308 |  | Recorded at baseline (day 1 of cycle 1), during each of the first 5 cycles (each cycle is 21 days or 28 days or 42 days) and up to the first 16 cycles of treatment (up to 22 months), and 30 and 90 days post last dose (up to approximately 25 months) | 
| Percentage of participants with anti-drug antibodies to zimberelimab |  | Recorded at baseline (day 1 of cycle 1), during each of the first 5 cycles (each cycle is 21 days or 28 days or 42 days) and up to the first 16 cycles of treatment (up to 22 months), and 30 and 90 days post last dose (up to approximately 25 months) | 
| Percentage of participants with Objective Response |  | From study enrollment until participant discontinuation, first occurrence of progressive disease, or death from any cause, whichever occurs first (up to approximately 3-5 years) | 
| Duration of Response |  | From the date of first occurrence of a documented objective response to first documentation of disease progression or death from any cause, whichever occurs first (up to approximately 3-5 years) | 
| Percentage of Participants with Disease Control (complete response, partial response, or stable disease) for >6 months |  | From study enrollment until disease progression or loss of clinical benefit (up to approximately 3-5 years) |