A First in Human Study of AdAPT-001 in Subjects With Refractory Solid Tumors (BETA-PRIME)

• ClinicalTrials.gov Identifier: NCT04673942
• Recruitment Status: Recruiting
• First Posted: December 17, 2020
• Last Update Posted: March 5, 2021
• Sponsor: EpicentRx, Inc.
• Information provided by (Responsible Party): EpicentRx, Inc.

Study Description

Brief Summary:

This is the first clinical trial of AdAPT-001 for the treatment of cancer. AdAPT-001 is an oncolytic virus that is injected directly into the tumor. The purpose of this study is to find out the highest dose of AdAPT-001 that is safe and tolerable. This is the first step in studying whether it can be used to treat others with cancer in the future.

Condition or disease	Intervention/treatment	Phase
Solid Tumor, Adult; Cancer; Neoplasms	Biological: AdAPT-001	Phase 1

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 2 parts. Different groups of patients will participate in each part.

PART 1: Dose Escalation Safety Run-In

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.

PART 2: Dose Expansion Single-Agent

All participants in PART 2 will receive injections of AdAPT-001 on Days 1 and 15 of 28-day cycles. The dose of AdAPT-001 used in Part 2 will be decided by the results from Part 1.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: 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).
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I, First in Human, Study to Evaluate the Safety and Tolerability of AdAPT-001 in Subjects With Refractory Solid Tumors
• Estimated Study Start Date: March 15, 2021
• Estimated Primary Completion Date: June 1, 2021
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part 1: Dose Escalation Safety Run-In; Subjects will be treated with AdAPT-001 as a single injection, one time.	Biological: AdAPT-001; Oncolytic virus administered by intratumoral injection
Experimental: Part 2: Dose Expansion Single-Agent; 6 subjects will be enrolled in the Lead In Cohort. A Safety Analysis will be performed after 6 subjects have received at least 4 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; Oncolytic virus administered by intratumoral injection

Outcome Measures

Primary Outcome Measures :

1. Dose Limiting Toxicities (DLT) [ Time Frame: 28 days ]
   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.
2. Maximum tolerated dose [ Time Frame: 28 days ]
   In part 1, A MTD is determined if any cohort experiences 2 subjects with DLT's.
3. Safety of a multiple dose regimen of AdAPT-001 [ Time Frame: 6 months ]
   The safety data will include adverse events, serious adverse events, performance status, clinical laboratory tests, vital signs and physical examination results.

Secondary Outcome Measures :

1. Anti-tumor activity of AdAPT-001 [ Time Frame: 6 months ]
   In part 2, 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.

Other Outcome Measures:

1. Anti-tumor activity by iRECIST [ Time Frame: 6 months ]
   ORR and best overall response rates per Immune Response Evaluation Criteria in Solid Tumors (iRECIST)
2. Biodistribution [ Time Frame: 6 months ]
   This outcome will measure TGFβ trap concentrations in the serum and, in patients who consent to tissue collections, test for TGFβ trap expression in the treated tumors.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 for treatment.
4. Subject's Eastern Cooperative Group (ECOG) performance status is 0-2 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) > 10.0 g/dL; > 6.2 mmol/L
8. Subject has an INR < 1.5
9. If subject has archival tissue formalin-fixed paraffin-embedded block(s) or previously cut archival tissue, submit 1 H&E slide and 5 unstained slides.
10. 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.
11. Subject is willing and able to comply with all protocol procedures, evaluations and rescue measures.

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 active bacterial, fungal, or viral infection. No subjects with an active SARS-CoV-2 infection (within 21 days of a positive test).
3. Known positive human immunodeficiency virus (HIV)
4. Known history of hepatitis B or C. Patients with a known history of hepatitis B or C will be eligible only if they have an undetectable viral load during screening.
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 having a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study agent administration. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) is allowed.
7. Prior adenoviral therapy for any indication except vaccination against infectious disease. If subject received a COVID-19 vaccination, cannot start treatment until 14 days after completing the vaccination series. Recommend waiting at least 28 days from AdAPT-001 dose prior to receiving COVID-19 vaccination (end of 28 Day Follow Up visit in Part 1).
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.

Contacts and Locations

Contacts

Contact: Jeannie Williams; 858-947-6644; jwilliams@epicentrx.com

Locations

United States, California

California Cancer Associates for Research and Excellence, cCARE; Recruiting

San Marcos, California, United States, 92069

Contact: Alberto Bessudo, MD 760-747-8935

Principal Investigator: Alberto Bessudo, MD

Providence Saint John's Health Center; Recruiting

Santa Monica, California, United States, 90404

Contact: Ashley Archer, CRA III 310-582-7467 archerA@jwci.org

Contact: Annie Heng, CRN 310-582-7457 henga@jwci.org

Principal Investigator: Santosh Kesari, MD PhD

Sponsors and Collaborators

EpicentRx, Inc.

Investigators

• Study Director: Bryan Oronsky, MD PhD; EpicentRx, Inc.

More Information

• Responsible Party: EpicentRx, Inc.
• ClinicalTrials.gov Identifier: NCT04673942
• Other Study ID Numbers: BETA-PRIME
• First Posted: December 17, 2020
• Last Update Posted: March 5, 2021
• Last Verified: March 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by EpicentRx, Inc.:

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

Additional relevant MeSH terms:

Neoplasms