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

NCT ID: NCT04673942

Last Updated: 2024-10-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-29
• Study Completion Date: 2027-03-01

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.

Detailed Description

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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

Group Type: EXPERIMENTAL

AdAPT-001

Intervention Type: BIOLOGICAL

Oncolytic virus administered by intratumoral injection

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

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.

Group Type: EXPERIMENTAL

AdAPT-001

Intervention Type: BIOLOGICAL

Oncolytic virus administered by intratumoral injection

PART 3: Expansion (Enrollment Completed)

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.

Group Type: EXPERIMENTAL

AdAPT-001

Intervention Type: BIOLOGICAL

Oncolytic virus administered by intratumoral injection

Checkpoint Inhibitor, Immune

Intervention Type: DRUG

Checkpoint Inhibitor per investigator discretion based on diagnosis and subject tolerability

Phase 2 (Enrollment Open)

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..

Group Type: EXPERIMENTAL

AdAPT-001

Intervention Type: BIOLOGICAL

Oncolytic virus administered by intratumoral injection

Checkpoint Inhibitor, Immune

Intervention Type: DRUG

Checkpoint Inhibitor per investigator discretion based on diagnosis and subject tolerability

Interventions

AdAPT-001

Oncolytic virus administered by intratumoral injection

Intervention Type: BIOLOGICAL

Checkpoint Inhibitor, Immune

Checkpoint Inhibitor per investigator discretion based on diagnosis and subject tolerability

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Subject is capable of understanding the purpose and risks of the study and has provided written Informed Consent.

2. Subject is male or female, aged at least 18 years.

3. 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.

4. Subject's Eastern Cooperative Group (ECOG) performance status is 0-1 at Screening.

5. Subject has acceptable liver function at Screening, as evidenced by:

1. Bilirubin < 1.5 x ULN (upper limit of normal)

2. AST (SGOT) and ALT (SGPT) < 3.0 x ULN (upper limit of normal)

3. Alkaline Phosphatase < 2.5 x ULN (upper limit of normal)

6. Subject has a Serum Creatinine < 1.5 x ULN (upper limit of normal)

7. Subject has acceptable hematologic status at Screening, as evidenced by:

1. Absolute neutrophil count > 1,500 cells/mm3; > 1.5 x 109/L, and

2. Platelet count > 75,000/mm3; > 75.0 x 109/L, and

3. Hemoglobin (HGB) ≥ 8.0 g/dL; ≥ 5.6 mmol/L

8. Subject has an INR < 1.5

9. 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.

10. Subject is willing and able to comply with all protocol procedures, evaluations and rescue measures.

11. OPTIONAL: Archival formalin-fixed paraffin-embedded block(s) or previously cut archival tissue for at least 5 unstained slides (if available).

Exclusion Criteria

1. 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.

2. 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)

3. Known positive history of human immunodeficiency virus (HIV) test

4. Subjects who have active hepatitis.

5. If female, subject is pregnant and/or breastfeeding.

6. 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.

7. 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.

8. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EpicentRx, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bryan Oronsky, MD PhD

Role: STUDY_DIRECTOR

EpicentRx, Inc.

Locations

City of Hope

Duarte, California, United States

Site Status: ACTIVE_NOT_RECRUITING

California Cancer Associates for Research and Excellence, cCARE

San Marcos, California, United States

Site Status: ACTIVE_NOT_RECRUITING

Providence Saint John's Health Center

Santa Monica, California, United States

Site Status: ACTIVE_NOT_RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status: RECRUITING

Mary Crowley Cancer Research

Dallas, Texas, United States

Site Status: ACTIVE_NOT_RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jeannie Williams

Role: CONTACT

info@epicentrx.com

858-947-6644

Facility Contacts

Cancer Answer

Role: primary

216-444-7923

Brielle Eble

Role: backup

Anthony P Conley, MD

Role: primary

References

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.

Reference Type: DERIVED

PMID: 39461878 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35950603 (View on PubMed)

Other Identifiers

BETA-PRIME

Identifier Type: -

Identifier Source: org_study_id