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 (also referred to as AIM-001) is an investigational, replication-competent type 5 oncolytic adenovirus engineered to express a transforming growth factor-β (TGF-β) trap. It is being developed for intratumoral administration in refractory solid tumors, as monotherapy and in combination with immune checkpoint inhibitors (ICIs). A first-in-human Phase 1 trial has been published, and a Phase 1/2 expansion (BETA PRIME) with optional ICI has reported interim results at ASCO 2024. (doi.org)

Mechanism of action

• Vector/design: Ad5 backbone with a targeted 50 bp deletion in the E1A promoter to restrict replication in normal cells and insertion of a TGF-β receptor–IgG Fc fusion “trap” transgene in the E1B-19K region. The trap binds and neutralizes TGF-β1 and TGF-β3 (not TGF-β2). (doi.org)
• Antitumor effects: Direct lysis of infected tumor cells plus immunomodulation via TGF-β blockade intended to convert “cold” tumors to “hot,” potentially enhancing responses to ICIs and enabling abscopal effects. Preclinical biodistribution shows systemic persistence of the trap after intratumoral dosing. (doi.org)

Efficacy

• Phase 1 monotherapy (BETA PRIME; n=28 across Parts 1–2): At the recommended Phase 2 dose (RP2D) of 1×10^12 viral particles intratumorally every 2 weeks, confirmed partial responses (3 patients) and durable stable disease ≥6 months (5 patients) were observed; antitumor activity was seen in injected and uninjected lesions. (doi.org)
• Phase 1/2 with/without ICI (ASCO 2024 interim; enrolled n=36, evaluable n=33):
• Monotherapy (n=9 evaluable): CR 1 (eccrine carcinoma), confirmed PR 1 (acral melanoma); clinical benefit rate (CBR: CR/PR/SD ≥12 weeks) 44.4% (4/9).
• Combination with ICI (n=24 evaluable): clinical CR 1 (angiosarcoma) and 6 confirmed PRs (3 sarcomas, 1 TNBC, 1 head and neck cancer, 1 SCC); CBR 62.5% (15/24).
• Median PFS 3.5 months (95% CI 1.8–NA). Many patients had prior ICI failure. (ascopubs.org)

Note: The Phase 1/2 results are interim meeting-abstract data; a full peer‑reviewed report of the combination cohort has not yet been published as of October 7, 2025. (ascopubs.org)

Safety

• Phase 1 monotherapy: No dose-limiting toxicities or treatment‑related serious adverse events; most adverse events were low grade (local inflammation, fever, fatigue). RP2D established at 1×10^12 viral particles every 2 weeks. (doi.org)
• Phase 1/2 interim (± ICI): Most common treatment‑related AEs were transient flu‑like symptoms and injection‑site events (each ~28%). Only one immune-related AE was reported (hypophysitis; ~4%) among combination‑treated patients; otherwise AEs were grade 1–2. (ascopubs.org)
• Nonclinical safety/biodistribution: In mice, single intratumoral or intravenous administration led to measurable systemic TGF‑β trap without TGF‑β–related toxicity at clinically relevant exposures. (pubmed.ncbi.nlm.nih.gov)

Development status and dosing

• Trial program: BETA PRIME first‑in‑human study with dose escalation, dose expansion (monotherapy), and an expansion cohort allowing addition of ICIs at investigator discretion (NCT04673942). (pubmed.ncbi.nlm.nih.gov)
• Dosing used clinically to date: intratumoral injection at 1×10^12 viral particles every 2 weeks (RP2D). (doi.org)

Further reading

• Peer‑reviewed Phase 1 results (monotherapy): Cancer Gene Therapy (2024). (doi.org)
• ASCO 2024 oral abstract (Phase 1/2 ± ICI): Journal of Clinical Oncology abstract 2506. (ascopubs.org)
• Trial design/protocol description: Future Oncology (2022). (pubmed.ncbi.nlm.nih.gov)
• Nonclinical toxicology/biodistribution: American Journal of Cancer Research (2021). (pubmed.ncbi.nlm.nih.gov)
• IND clearance and alternative name (AIM‑001): Business Wire (2020). (businesswire.com)

This summary reflects evidence available online as of October 7, 2025.

Last updated: Oct 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.