An Adapted Phase 2a/2b, Study to Evaluate the Safety, Tolerability, and Efficacy of AdAPT-001 in Subjects With Refractory Solid Tumors

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.

More details:

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.

Overview

AdAPT-001 (AIM-001) is an investigational oncolytic adenovirus engineered to replicate selectively in tumor cells and to express a transforming growth factor-β (TGF-β) “trap.” It is being studied primarily via intratumoral injection, alone or in combination with immune checkpoint inhibitors (ICIs), in patients with refractory solid tumors including soft-tissue sarcoma (STS). A Phase 1 first‑in‑human study reported antitumor activity with a favorable safety profile and recommended a Phase 2 dose of 1.0 × 10^12 viral particles every 2 weeks. A multicenter Phase 2 trial is ongoing; early results presented at ASCO 2024 described objective responses with AdAPT-001 alone and in combination with an ICI in largely ICI‑refractory populations. The program has FDA Fast Track designation for recurrent or refractory advanced/metastatic STS in combination with nivolumab or atezolizumab. (pmc.ncbi.nlm.nih.gov, tandfonline.com, pubmed.ncbi.nlm.nih.gov, ascopubs.org, epicentrx.com)

Mechanism of action

• Vector/backbone: Conditionally replicative human adenovirus serotype 5 with a 50‑bp deletion in the E1A promoter that restricts productive replication to transformed cells. (tandfonline.com)
• Transgene: Secreted TGF‑β trap (soluble TGF‑β receptor II fused to human IgG1 Fc) designed to neutralize TGF‑β isoforms 1 and 3 within the tumor microenvironment, thereby reducing immunosuppression and fibrosis and potentially enhancing ICI responsiveness. (tandfonline.com, pmc.ncbi.nlm.nih.gov)
• Functional effects: Direct oncolysis from viral replication plus immunomodulation (increasing CD8+ T‑cell infiltration, shifting macrophage/T‑cell phenotypes toward Th1/M1, and eliciting abscopal responses in preclinical models). (pmc.ncbi.nlm.nih.gov, tandfonline.com)

Efficacy

Human studies (as of September 2, 2025):

• Phase 1 (BETA prime; Cancer Gene Therapy 2024): In 28 evaluable patients with advanced refractory solid tumors treated intratumorally (single‑dose escalation then multidose expansion), confirmed partial responses (PRs) occurred in 3 patients; 5 additional patients had durable stable disease ≥6 months. Evidence of activity was observed in injected and uninjected lesions. (pmc.ncbi.nlm.nih.gov)
• Phase 2 (ASCO 2024 abstract; NCT04673942): Among 33 evaluable patients enrolled Feb–Dec 2023, monotherapy produced 2/9 responses (22.2%: 1 complete response [CR] in eccrine carcinoma; 1 confirmed PR in acral melanoma) with a 44.4% clinical benefit rate (CBR, CR/PR/SD >12 weeks). AdAPT-001 plus an ICI yielded 7/24 responses (29.1%: 1 clinical CR in angiosarcoma; 6 confirmed PRs across sarcoma, triple‑negative breast cancer, head and neck cancer, and cutaneous squamous cell carcinoma) and a 62.5% CBR; notably, 5/16 (31.2%) ICI‑refractory patients responded. Reported median PFS was 3.5 months (95% CI 1.8–not estimable). (ascopubs.org)

Trial status/design notes: The first‑in‑human trial (NCT04673942) progressed from Phase 1 to an open Phase 2 basket evaluating AdAPT‑001 with or without an ICI; dosing is intratumoral every 2 weeks, with investigator‑discretion ICI choice in combination cohorts. (ctv.veeva.com, centerwatch.com, trial.medpath.com)

Regulatory: FDA Fast Track designation (December 5, 2024) for AdAPT‑001 plus nivolumab or atezolizumab in recurrent or refractory advanced/metastatic STS after at least one prior therapy. (epicentrx.com)

Safety

• Phase 1: No dose‑limiting toxicities, no treatment‑related serious adverse events, and no grade 4 toxicities were reported. Common adverse events were local inflammatory reactions, transient fever, and fatigue. (pmc.ncbi.nlm.nih.gov)
• Phase 2 (ASCO 2024 abstract): Most treatment‑related AEs were grade 1–2 flu‑like symptoms (fever, chills, vomiting, fatigue) and injection‑site events (each 27.7%). Immune‑related AEs were uncommon; 1/24 (4.0%) in the combination cohort developed hypophysitis. (ascopubs.org)

Further reading

• BETA prime: first‑in‑human Phase 1 results (Cancer Gene Therapy, 2024). (pmc.ncbi.nlm.nih.gov)
• Phase 2 ASCO 2024 abstract with monotherapy and combination outcomes. (ascopubs.org)
• Study protocol/rationale for the BETA PRIME trial (Future Oncology, 2022). (tandfonline.com)
• Preclinical study showing TGF‑β trap mechanism and synergy with anti‑PD‑L1. (pmc.ncbi.nlm.nih.gov)
• Toxicology and biodistribution of AdAPT‑001 (replication‑competent Ad5 with TGF‑β trap). (pmc.ncbi.nlm.nih.gov)
• Trial listing and status for NCT04673942. (centerwatch.com, ctv.veeva.com)
• Company announcement of FDA Fast Track designation in STS. (epicentrx.com)

Notes - Data are from early-phase studies with limited patient numbers; confirmatory randomized data are not yet available. Findings from conference abstracts are preliminary and subject to change upon full publication. (ascopubs.org)

Last updated: Sep 2025

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.