AdAPT-001 is an oncolytic virus that is injected directly into the tumor or via intraarterial administration. The purpose of this study is to find out if AdAPT-001 is safe and tolerable. The next step is to find out if AdAPT-001 if efficacious with or without a checkpoint inhibitor.
This is a dose escalation protocol to determine, first and foremost, the safety, tolerability and feasibility of intratumoral administration of AdAPT-001. The study has 3 parts. Different groups of patients will participate in each part. PHASE 1 PART 1: Dose Escalation Safety Run-In (CLOSED - Enrollment Completed) During PART 1, all participants will be treated with AdAPT-001 as a single injection, one time. Participants will be assigned to different dose levels to find the highest dose of AdAPT-001 that is safe and tolerable. PHASE 1 PART 2: Dose Expansion Single-Agent (CLOSED - Enrollment Completed) All participants in PART 2 will receive injections of AdAPT-001 on Days 1 and 15 of 28-day cycles. PHASE 1 PART 3: Expansion (CLOSED - Enrollment Completed) Subjects will be assigned to the following two arms. If a checkpoint inhibitor is indicated for the subject, the subject may be enrolled on Arm 2 per investigator discretion, otherwise subjects may be enrolled on Arm 1. Arm 1: Intratumoral administration of AdAPT-001 (1.0 x 10¹² viral particles) on Day 1 and 15 of each 28-day cycle for up to 12 injections. Arm 2: Intratumoral administration of AdAPT-001 (1.0 x 10¹² viral particles) on Day 1 and 15 of each 28-day cycle for up to 12 injections plus a checkpoint inhibitor per investigator discretion PHASE 2: (OPEN to Enrollment) Subjects with advanced solid tumors will participate in a basket two-arm parallel group evaluation (Phase 2) where eligible participants will be assigned to the following two arms based on confirmed histology by the treating investigator. Arm 1: Confirmed Histological Diagnosis of Sarcoma Intratumoral Administration of AdAPT-001 (1.0 x 10¹² viral particles) on Day 1 and 15 of each 28-day cycle for up to 12 injections with or without a checkpoint inhibitor. Arm 2: Confirmed Histological Diagnosis of Advanced Solid Tumor indicated to receive at least one checkpoint inhibitor.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Oncolytic virus administered by intratumoral injection
Checkpoint Inhibitor per investigator discretion based on diagnosis and subject tolerability
City of Hope
Duarte, California, United States
California Cancer Associates for Research and Excellence, cCARE
San Marcos, California, United States
Providence Saint John's Health Center
Santa Monica, California, United States
Cleveland Clinic
Cleveland, Ohio, United States
Dose Limiting Toxicities (DLT)
All subjects in PART 1 will be assessed for the development of dose-limiting toxicity (DLT) during treatment with AdAPT-001. The DLT assessment period is defined as: Day of Injection through 28 days post injection (Safety Follow Up). A DLT will be defined as any Grade 3 or higher adverse event, as assessed by the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: 28 days
Maximum tolerated dose
In PART 1, A MTD is determined if any cohort experiences 2 subjects with DLT's.
Time frame: 28 days
Safety of a multiple dose regimen of AdAPT-001
The safety data will include adverse events, serious adverse events, performance status, clinical laboratory tests, vital signs and physical examination results.
Time frame: 6 months
Anti-tumor activity of the two-arm dose regimens of AdAPT-001 in Phase 2
To evaluate the efficacy of the two-arm dose regimens of AdAPT-001 in subjects with advanced solid tumors that have progressed after treatment with standard therapies or for which there are no appropriate therapies available as measured by durable (≥4 months) stable disease per Response Evaluation Criteria in Solid Tumors (RECIST).
Time frame: 6 months
Anti-tumor activity of AdAPT-001
In PART 2 and PART 3, overall response rate (ORR) and best overall response rates per response evaluation criteria outlined in Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1), as well as progression-free survival (PFS), and duration of response will be assessed.
Time frame: 6 months
Objective response rate
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Masking
NONE
Enrollment
140
Mary Crowley Cancer Research
Dallas, Texas, United States
MD Anderson Cancer Center
Houston, Texas, United States
Preliminarily to assess anti-tumor activity of AdAPT-001 by objective response rates (ORR) and best overall response rates per response evaluation criteria outlined in RECIST guideline (Version 1.1),
Time frame: 6 months