A Study of AdAPT-001 in Subjects With Sarcoma and Refractory Solid Tumors

NCT04673942 | Recruiting Phase 2 FDA Drug

• 1 other identifier: BETA-PRIME
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Solid Tumor, Adult; Cancer; Neoplasms; Sarcoma; Sarcoma,Soft Tissue; Chondrosarcoma

Keywords

oncolytic virus; immunotherapy; adenovirus; intratumoral injection; AdAPT-001; Sarcoma

Outcome Measures

Primary Outcomes (4)

• 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.

  28 days

• Maximum tolerated dose

  In PART 1, A MTD is determined if any cohort experiences 2 subjects with DLT's.

  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.

  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).

  6 months

Secondary Outcomes (2)

• Anti-tumor activity of AdAPT-001

  6 months

• Objective response rate

  6 months

Other Outcomes (2)

• Anti-tumor activity by iRECIST

  6 months

• Biodistribution

  6 months

Study Arms (4)

PART 1: Dose Escalation Safety Run-In (Enrollment Completed)

EXPERIMENTAL

Subjects will be treated with AdAPT-001 as a single injection, one time.

Biological: AdAPT-001

PART 2: Dose Expansion Single-Agent (Enrollment Completed)

EXPERIMENTAL

6 subjects will be enrolled in the Lead In Cohort. A Safety Analysis will be performed after 6 subjects have received at least 24 doses. Upon Safety team review as a continuous reassessment of safety, an additional 19 subjects may be enrolled. All subjects in PART 2 will receive injections of AdAPT-001 on Days 1 and 15 of 28-day cycles.

Biological: AdAPT-001

PART 3: Expansion (Enrollment Completed)

EXPERIMENTAL

Up to 45 subjects will be enrolled in the expansion cohort to receive either AdAPT-001 on Days 1 and 15 of 28-day cycles or AdAPT-001 on Days 1 and 15 plus a checkpoint inhibitor of 28-day cycles.

Biological: AdAPT-001; Drug: Checkpoint Inhibitor, Immune

Phase 2 (Enrollment Open)

EXPERIMENTAL

Approximately 55 to 80 subjects with advanced solid tumors including sarcoma to receive either AdAPT-001 on Days 1 and 15 of 28-day cycles or AdAPT-001 on Days 1 and 15 plus a checkpoint inhibitor of 28-day cycles..

Biological: AdAPT-001; Drug: Checkpoint Inhibitor, Immune

Interventions

AdAPT-001 BIOLOGICAL

Oncolytic virus administered by intratumoral injection

PART 1: Dose Escalation Safety Run-In (Enrollment Completed); PART 2: Dose Expansion Single-Agent (Enrollment Completed); PART 3: Expansion (Enrollment Completed); Phase 2 (Enrollment Open)

Checkpoint Inhibitor, Immune DRUG

Checkpoint Inhibitor per investigator discretion based on diagnosis and subject tolerability

PART 3: Expansion (Enrollment Completed); Phase 2 (Enrollment Open)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is capable of understanding the purpose and risks of the study and has provided written Informed Consent.
• Subject is male or female, aged at least 18 years.
• Subject has a histologically or cytologically confirmed diagnosis of an advanced malignant solid tumor(s) who have received all conventional therapies considered appropriate by Investigator and have a tumor that is easily accessible and/or palpable for treatment. Ultrasound guidance may be used to aid administration.
• Subject's Eastern Cooperative Group (ECOG) performance status is 0-1 at Screening.
• Subject has acceptable liver function at Screening, as evidenced by:
• Bilirubin \< 1.5 x ULN (upper limit of normal)
• AST (SGOT) and ALT (SGPT) \< 3.0 x ULN (upper limit of normal)
• Alkaline Phosphatase \< 2.5 x ULN (upper limit of normal)
• Subject has a Serum Creatinine \< 1.5 x ULN (upper limit of normal)
• Subject has acceptable hematologic status at Screening, as evidenced by:
• Absolute neutrophil count \> 1,500 cells/mm3; \> 1.5 x 109/L, and
• Platelet count \> 75,000/mm3; \> 75.0 x 109/L, and
• Hemoglobin (HGB) ≥ 8.0 g/dL; ≥ 5.6 mmol/L
• Subject has an INR \< 1.5
• Female subjects of childbearing potential (i.e., women who have not been surgically sterilized or have not been post-menopausal for at least one year), and male subjects with partners of childbearing potential, must agree to use medically acceptable methods of contraception beginning on Study Day 1 and continuing until at least four weeks after administration of the subject's final dose of AdAPT-001. Medically acceptable contraception is defined as either: 1) usage by at least one of the partners of a barrier method of contraception, together with usage by the female partner, commencing at least three months prior to Study Day 1, of a stable regimen of any form of hormonal contraception or an intra-uterine device, or 2) usage by the couple of a double-barrier method of contraception. Use of a single-barrier method alone or abstinence alone is not considered adequate.

You may not qualify if:

• Presence of a serious co-morbid medical condition, or a clinically significant laboratory finding(s) that, in the opinion of the Investigator, suggests the presence of an infectious, endocrine, and/or other inadequately treated systemic disorder.
• A known uncontrolled active bacterial, fungal, or viral infection. No subject with an active SARS-CoV-2 infection (within 14 days of a positive test)
• Known positive history of human immunodeficiency virus (HIV) test
• Subjects who have active hepatitis.
• If female, subject is pregnant and/or breastfeeding.
• Subjects with active autoimmune disease or history of autoimmune disease that might recur and may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded.
• Note: Subjects in any condition requiring systemic treatment with corticosteroids (prednisone \> 10 mg/day or equivalent of the similar drug) or other immunosuppressive agents within 14 days before AdAPT-001), but currently or previously treated with any of the following steroid regimens were included: Topical, ophthalmic, intra-articular, intranasal, or inhaled corticosteroids with minimal systemic absorption; prophylactic short-term use of corticosteroids.
• Prior adenoviral therapy for any indication except vaccination against infectious disease. Subjects receiving COVID-19 or live vaccination, cannot start treatment until 7 days after completing the vaccination. Recommend waiting at least 28 days from AdAPT-001 dose prior to receiving COVID-19 vaccination. Concurrent treatment with Evusheld is allowed.
• Chemotherapy or immunotherapy within 14 days of study treatment. Hormonal therapy (including tamoxifen, aromatase inhibitors, and gonadotropin releasing hormone agonists) is allowed. Concurrent treatment with bisphosphonate and RANK ligand inhibitor is allowed.

Sponsors & Collaborators

• EpicentRx, Inc.: lead

Study Sites (6)

City of Hope

Duarte, California, 91010, United States

ACTIVE NOT RECRUITING

California Cancer Associates for Research and Excellence, cCARE

San Marcos, California, 92069, United States

ACTIVE NOT RECRUITING

Providence Saint John's Health Center

Santa Monica, California, 90404, United States

ACTIVE NOT RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

ACTIVE NOT RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Publications (2)

• Reid TR, Oronsky B, Williams J, Caroen S, Conley A. TGF-beta trap of AdAPT-001 turns up the heat on tumors and turns down checkpoint blocker resistance. J Immunother Cancer. 2024 Oct 26;12(10):e009613. doi: 10.1136/jitc-2024-009613.

  PMID: 39461878 DERIVED

• Kesari S, Bessudo A, Gastman BR, Conley AP, Villaflor VM, Nabell LM, Madere D, Chacon E, Spencer C, Li L, Larson C, Reid T, Caroen S, Oronsky B, Stirn M, Williams J, Barve MA. BETA PRIME: Phase I study of AdAPT-001 as monotherapy and combined with a checkpoint inhibitor in superficially accessible, treatment-refractory solid tumors. Future Oncol. 2022 Sep;18(29):3245-3254. doi: 10.2217/fon-2022-0481. Epub 2022 Aug 11.

  PMID: 35950603 DERIVED

MeSH Terms

Conditions

Neoplasms; Sarcoma; Chondrosarcoma; Adenoviridae Infections

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms, Connective Tissue; DNA Virus Infections; Virus Diseases; Infections

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Bryan Oronsky, MD PhD

  EpicentRx, Inc.

  STUDY DIRECTOR

Central Study Contacts

Jeannie Williams

CONTACT

858-947-6644; info@epicentrx.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study is an exploratory open label single-arm interventional study using a 3 + 3 dose escalation safety run-in (PART 1) followed by a dose expansion single-agent (PART 2), followed by expansion (PART 3) single agent or single agent plus checkpoint inhibitor, followed by an adaptive designed Phase 2..

Study Record Dates

• First Submitted: December 8, 2020
• First Posted: December 17, 2020
• Study Start: March 29, 2021
• Primary Completion: December 1, 2025
• Study Completion (Estimated): March 1, 2027
• Last Updated: October 26, 2024

Record last verified: 2024-10

Locations

US (6)