A Study of AB801 Monotherapy and Combination Therapy in Participants With Advanced Malignancies

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 AB801 in participants with advanced malignancies, and to determine a recommended AB801 dose for expansion.

Official Title
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A Phase 1/1b Study to Evaluate the Safety and Tolerability of AB801 Monotherapy and Combination Therapy in Participants With Advanced Malignancies

Conditions
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Advanced Cancer

Intervention / Treatment
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* Drug: AB801
* Drug: Zimberelimab
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Monotherapy-specific criteria for dose escalation cohorts: Participants may have cytologically or pathologically confirmed non-small cell lung carcinoma (NSCLC), colorectal carcinoma (CRC), breast, ovarian, renal cell carcinoma (RCC), head and neck squamous cell carcinoma (HNSCC), or bladder carcinoma that has progressed or was non-responsive to available therapies with no standard of care (SOC) options, or for whom standard therapy has proven ineffective, intolerable, or considered inappropriate; or for whom a clinical study of an investigational agent is a recognized SOC. Disease-specific criteria for dose-expansion Cohort 1 (STK11m [mutated or deleted] NSCLC): Cytologically or pathologically confirmed locally advanced unresectable or metastatic (Stage IIIB-IV per American Joint Committee on Cancer [AJCC] version 8) non-squamous NSCLC with documented mutation or deletion in the STK11 gene. Negative for actionable mutations including epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), mesenchymal-epithelial transition factor (C-MET) or ret proto-oncogene (RET). Mixed small-cell lung carcinoma (SCLC) and squamous NSCLC histology is not permitted. Previously treated in the unresectable locally advanced or metastatic setting with a platinum-containing chemotherapy and programmed cell death ligand-1 (PD-L1) inhibitor. Disease-specific criteria for dose-expansion Cohort 2 (NSCLC): Cytologically or pathologically confirmed locally advanced unresectable or metastatic (Stage IIIB-IV per American Joint Committee on Cancer version 8) non-squamous NSCLC negative for actionable mutations in EGFR, ALK, ROS1, NTRK, C-MET, or RET. Mixed SCLC and squamous NSCLC histology is not permitted. Previously treated in the unresectable locally advanced or metastatic setting with a platinum-containing chemotherapy and PD-(L)-1inhibitor. Must have at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) guidance (Version 1.1) (Section 1.1). The measurable lesion must be outside of a radiation field if the participant received prior radiation unless discussed and approved by the study physician. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. Key Exclusion Criteria: Use of any live vaccines against infectious diseases (eg, influenza, varicella) within 4 weeks (28 days) of initiation of investigational product. Underlying medical conditions or adverse events that, in the physician or sponsor's opinion, will make the administration of investigational products hazardous. Prolonged QT interval defined as mean corrected QT interval (QTc) ≥ 450 milliseconds (ms). 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. Treatment with systemic immunosuppressive medication (including but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumor necrosis factor-α agents) administered within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressant medication during study treatment. 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 Cohort 1 - AB801 Dose Level 1<br>Participants will receive AB801 orally daily | Drug: AB801<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Escalation Cohort 2 - AB801 Dose Level 2<br>Participants will receive AB801 orally daily | Drug: AB801<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Escalation Cohort 3 - AB801 Dose Level 3<br>Participants will receive AB801 orally daily | Drug: AB801<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Escalation Cohort 4 - AB801 Dose Level 4<br>Participants will receive AB801 orally daily | Drug: AB801<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Escalation Cohort 5 - AB801 Dose Level 5<br>Participants will receive AB801 orally daily | Drug: AB801<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Escalation Cohort 6 - AB801 Dose Level 6<br>Participants will receive AB801 orally daily | Drug: AB801<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Expansion Cohort 1- AB801 + Zimberelimab + Docetaxel<br>Participants with NSCLC with known mutation or deletion of serine/threonine kinase 11 gene will receive AB801 orally in combination with zimberelimab and docetaxel administered via intravenous (IV) infusion | Drug: AB801<br>* Administered as specified in the treatment arm<br>Drug: Zimberelimab<br>* Administered as specified in the treatment arm<br>Drug: Docetaxel<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Expansion Cohort 2 - AB801 + Docetaxel<br>Participants with NSCLC will receive AB801 orally in combination with docetaxel IV infusion | Drug: AB801<br>* Administered as specified in the treatment arm<br>Drug: Docetaxel<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 |  | 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 Plasma Drug Concentration-Time Curve (AUC) |  | Predose, Up to 8 hours postdose | 
| Maximum Concentration (Cmax) in Plasma |  | Predose, Up to 8 hours postdose | 
| Time to Maximum Concentration (Tmax) in Plasma |  | Predose, Up to 8 hours postdose | 
| Objective response rate (ORR) as Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |  | Up to 2 years | 
| Dose Expansion Cohorts: Duration of Response (DOR) as Assessed per RECIST v1.1 |  | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AB801, Non-small cell lung cancer (NSCLC)