AB-2100, an Integrated Circuit T (ICT) Cell Therapy in Patients with Recurrent Clear-cell Renal Cell Carcinoma (ccRCC)

Phase 1

Recruiting

• Conditions: Advanced/Metastatic Clear Cell Renal Cell Carcinoma; Recurrence
• Interventions: Biological: AB-2100

• Registration Number: NCT06245915
• Lead Sponsor: Arsenal Biosciences, Inc.

Brief Summary

This is a multi-center, open-label phase 1/2 trial evaluating the safety and efficacy of AB-2100 cell product. The study may enroll approximately 60 patients in phase 1 and approximately 70 patients in phase 2.

Detailed Description

This study is intended for the patients who have been diagnosed with clear-cell renal cell carcinoma that either came back or did not improve after treatment with a checkpoint inhibitor and a VEGF inhibitor. The purpose of this study is to test the safety and efficacy of using a new treatment called Integrated Circuit T (ICT) cells (AB-2100 cells) in patients with renal cell carcinoma. This treatment has not been approved by the Food and Drug Administration.

The goal of this study is to determine the maximum tolerated dose of the AB-2100 cells. T cells are part of the immune system that protect the body from infection and may help fight cancer. The T cells given in this study will come from the patient and will have a genetic circuit/logic gate put in them that makes them able to recognize prostate-specific membrane antigen (PSMA) and carbonic anhydrase 9 (CA9), 2 proteins found on tumor cells. These logic-gated T cells may help the body's immune system identify and kill cancer cells while sparing normal healthy tissues from toxicity.

The AB-2100 cells are given intravenously, after completing 3 rounds of conditioning chemotherapy administered over 3 consecutive days. Conditioning chemotherapy prepares the body to receive the AB-2100 cells. If they continue to meet the eligibility criteria, AB-2100 cells will be given to them 2 days after the last conditioning chemotherapy round. A single infusion of the AB-2100 cells will be given to the subject intravenously.

After completion of study treatment, patients are followed with serial measurements of safety, tolerability and response.

This is a research study to obtain new information that may help people in the future.

Study Timeline

• Study First Submitted: 2024-01-30
• Study First Submitted QC: 2024-02-06
• Study First Posted: 2024-02-07
• Study Start: 2024-02-26
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-06
• Last Update Posted: 2024-11-07
• Primary Completion: 2025-02-26
• Study Completion: 2027-05-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

• Advanced or metastatic clear-cell renal cell carcinoma
• Must have received an immune checkpoint inhibitor and a VEGF-targeted therapy in the advanced or metastatic setting. Must have evidence of progression on or after the last treatment regimen or discontinued treatment for unacceptable toxicity.
• Adequate organ function as per protocol definitions.
• Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1.
• Measurable disease at time of enrollment as per protocol definitions.
• Female subjects of childbearing potential and male subjects must agree to use acceptable method(s) of contraception from enrollment through at least 12 months after AB-2100 infusion.

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Exclusion Criteria

• Any prior systemic RCC therapy within 14 days of time of cell collection (interval of 28 days will be required if the last immediate treatment contained an antibody-based agent).
• Systemic anti-cancer therapy within 14 days of starting of conditioning chemotherapy (interval of 28 days will be required if the last immediate treatment contained an antibody-based agent)
• Investigational cellular therapies within 8 weeks prior to start of conditioning chemotherapy
• Prior treatment with anti-CA9 therapies
• Myocardial infarction or unstable angina within 6 months prior to screening
• Pleural effusion that requires drainage for symptom management within 28 days of screening.
• Active autoimmune disease requiring immunosuppressive therapy or uncontrolled with treatment.
• Untreated brain metastasis.
• Subjects unwilling to participate in an extended safety monitoring period.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AB-2100	AB-2100	Patients receive fludarabine and cyclophosphamide intravenously on days -5 to -3. Patients receive a single dose of AB-2100 intravenously on day 0.

Primary Outcome Measures

Name	Time	Method
Phase 1 (Dose escalation): incidence of adverse events	From AB-2100 infusion up to 21 days post infusion	Defined as dose-limiting toxicities based on a 3+3 dose escalation study design
Phase 2 (Cohort expansion): Objective response rate (ORR)	From AB-2100 infusion up to 24 months post-infusion	ORR based on Independent Review Committee (IRC) assessment, defined as the proportion of subjects who have achieved a best overall response of CR or PR according to RECIST v1.1

Trial Locations

Locations (7)

Dana Farber Cancer Institue; 🇺🇸 Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York City, New York, United States

Huntsman Cancer Institute - Univ of Utah Health; 🇺🇸 Salt Lake City, Utah, United States

City of Hope; 🇺🇸 Duarte, California, United States

University of Iowa and Holden Comprehensive Cancer Center; 🇺🇸 Iowa City, Iowa, United States

Perlmutter Cancer Center - NYU Langone Health; 🇺🇸 New York, New York, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States