A Phase 1 Study of AB521 in Renal Cell Carcinoma and Other Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of AB521 when taken alone in participants with advanced solid tumor malignancies and clear cell renal cell carcinoma (ccRCC).

Official Title
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A Phase 1, Open-label, Dose Escalation and Dose Expansion Study, to Investigate the Safety, Tolerability, and Pharmacokinetic Profile of AB521 Monotherapy in Participants With Clear Cell Renal Cell Carcinoma and Other Solid Tumors

Conditions
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Clear Cell Renal Cell Carcinoma, Solid Tumors

Intervention / Treatment
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* Drug: AB521


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Disease-specific criteria for dose escalation: Participants may have any pathologically confirmed solid tumor type where no other treatment options are available. Disease-specific criteria for dose-expansion: Histologically confirmed ccRCC, must have received prior treatment in the metastatic setting (either individually or in combination) with an anti-programmed cell death protein 1 (anti-PD-1) therapy and a tyrosine kinase inhibitor (TKI), and no prior treatment with a hypoxia inducible factor (HIF)-2 alpha (α)-targeting therapy. Must have at least one measurable lesion per RECIST guidance. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 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 that, in the investigator's judgment, will make the administration of investigational product hazardous (eg, interstitial lung disease, active infections requiring antibiotics, recent hospitalizations with unresolved symptoms) or obscure the interpretation of toxicity determination or AEs. History of trauma or major surgery within 28 days prior to the first dose of investigational product. For monotherapy dose expansion: prior treatment with an HIF-2α inhibitor. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 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<br>Participants will receive AB521 orally once daily | Drug: AB521<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Escalation Cohort 2<br>Participants will receive AB521 orally once daily | Drug: AB521<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Escalation Cohort 3<br>Participants will receive AB521 orally twice daily | Drug: AB521<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Escalation Cohort 4<br>Participants will receive AB521 orally | Drug: AB521<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Expansion Cohort 1<br>Participants will receive AB521 orally | Drug: AB521<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Expansion Cohort 2<br>Participants will receive AB521 orally | Drug: AB521<br>* Administered as specified in the treatment arm<br>|
| Experimental: Dose Expansion Cohort 3<br>Participants will receive AB521 orally | Drug: AB521<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 dose limiting toxicities (DLTs) |  | Up to 4 months | 
| Number of participants with adverse events (AEs) |  | Up to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate as measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |  | Up to 4 months | 
| Plasma concentration of AB521 |  | Up to 4 months | 
| Area under the plasma concentration time curve (AUC) of AB521 |  | Up to 4 months | 
| Maximum Observed Plasma Concentration (Cmax) of AB521 |  | Up to 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clear Cell Renal Cell Carcinoma, Solid Tumor Malignancies, Pharmacokinetics, Pharmacodynamics, AB521