AIM-001 / EpicentRx - LARVOL DELTA

AdAPT-001 demonstrates potent oncolytic activity, high levels of TGFβ inhibition, and encouraging clinical activity in refractory sarcoma: update of the BETA-PRIME trial and preclinical correlates (AACR 2025) - "Standard chemotherapy includes doxorubicin alone or with ifosfamide with high toxicity and low response rates. Other approved therapies in sarcoma are trabectedin, eribulin, and pazopanib, but their response rates are less than 10%...In the SARC028 phase 2 clinical trial, the PD-1 inhibitor, pembrolizumab, had limited activity except in undifferentiated pleomorphic sarcoma and liposarcoma. In the Phase 2 Alliance A091401 trial, the response to nivolumab was very low at only 5%, which led the investigators to arrive at a conclusion of medical futility, stating that, "Nivolumab alone does not warrant further study in an unselected sarcoma population given the limited efficacy"...To further understand the activity of AdAPT-001 in sarcoma, we analyzed the lytic activity, TGFβ trap expression, and checkpoint expression patterns of sarcoma cell lines after infection. We demonstrate robust infection, replication, lysis and high-levels of TGFβ trap expression in..."

IO biomarker • Preclinical • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma • TGFB1

Effect of AdAPT-001 on checkpoint inhibitor resistance in solid tumors. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT04673942 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Checkpoint inhibition • Oncology • Solid Tumor

AdAPT-001, a first-in-class 2-in-1 TGF-beta inhibitor plus a checkpoint inhibitor: updated results from a phase 2 study in solid tumors (SITC 2024) - P2 | "Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.View this table:View inline View popup Download powerpoint Abstract 663 Table 1 Download figure Open in new tab Download powerpoint Abstract 663 Figure 1 Complete clinical response of a patient with angiosarcoma of the face treated with AdAPT-001 + nivolumabDownload figure Open in new tab Download powerpoint Abstract 663 Figure 2 Complete response of a patient with angiosarcoma of the glabellaDownload figure Open in new tab Download powerpoint Abstract 663 Figure 3 Partial response of a patient with TNBC"

Checkpoint inhibition • P2 data • Angiosarcoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Triple Negative Breast Cancer • TGFB1

EpicentRx's Oncolytic Virus-delivered TGFβ Inhibitor, AdAPT-001, Receives FDA Fast Track Designation for Recurrent or Refractory Soft Tissue Sarcoma Treatment (PRNewswire) - "EpicentRx announced today that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for the oncolytic adenovirus-delivered transforming growth factor beta (TGFβ) inhibitor, AdAPT-001, plus the anti-PD-1, nivolumab, or anti-PD-L1, atezolizumab, to treat recurrent or refractory advanced or metastatic soft tissue sarcoma (STS) with disease progression after at least one prior line of therapy....Supporting evidence for Fast Track designation came from Phase 1 and 2 clinical trials and an ASCO podium presentation where the activity, safety, and durability of response (progression free survival of ~8.5 months) in patients with STS and other tumor types either alone or in combination with checkpoint inhibition were on full display."

Fast track • Soft Tissue Sarcoma

PHASE I/II STUDY OF THE TGF-BETA-TRAP ENHANCED ONCOLYTIC ADENOVIRUS, ADAPT-001, WITH AND WITHOUT AN IMMUNE CHECKPOINT INHIBITOR FOR SARCOMA PATIENTS (CTOS 2024) - No abstract available

Checkpoint inhibition • Clinical • Oncolytic virus • P1/2 data • Oncology • Sarcoma • Solid Tumor • TGFB1

TGF-β trap of AdAPT-001 turns up the heat on tumors and turns down checkpoint blocker resistance. (PubMed, J Immunother Cancer) - P2 | "AdAPT-001 is an oncolytic adenovirus that expresses a transforming growth factor beta (TGF-β) trap to neutralize active TGF-β. This editorial proposes that the TGF-β trap of AdAPT-001 reverses the immunosuppressive environment of tumor cells, and thus makes these tumors susceptible to CIs like the anti-PD-1 agent, nivolumab, and potentially other therapies as well."

Checkpoint block • Checkpoint inhibition • Journal • Oncology • TGFB1

Hypothesis: AdAPT-001 and pseudoprogression - when seeing is not necessarily believing. (PubMed, J Immunother Cancer) - P2 | "PsP has also been described and documented in the context of oncolytic virotherapy but perhaps to a lesser extent. However, repeated intratumoral injections with these immunostimulatory agents may induce a more intense immune response and release more antigenic epitopes than with ICIs, for example, which are strictly T-cell directed rather than also tumor-directed like AdAPT-001."

Journal • Brain Cancer • Fibrosis • Immunology • Oncology • Solid Tumor • TGFB1

Phase 1/2 study of the TGF-β-trap-enhanced oncolytic adenovirus, AdAPT-001, plus an immune checkpoint inhibitor for patients with immune refractory cancers. (ASCO 2024) - P2 | "Combination therapy of AdAPT-001 with a CI is well tolerated and demonstrates a high ORR including 1 patient with a CR per RECIST 1.1, 1 patient with a clinical CR and 6 PRs. In several cutaneous sarcomas treated with AdAPT-001 plus a CI, radiologic SD belied how much better they looked visually--not only smaller, but less irregular and more circumscribed."

Checkpoint inhibition • Clinical • Oncolytic virus • P1/2 data • Angiosarcoma • Breast Cancer • Fatigue • Head and Neck Cancer • Melanoma • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Triple Negative Breast Cancer • TGFB1

EpicentRx Announces Oral Presentation for the Most Clinically Advanced TGF-β Ligand Trap, AdAPT-001, at the Upcoming 2024 ASCO Annual Meeting (PRNewswire) - P2 | N=140 | BETA PRIME (NCT04673942) | Sponsor: EpicentRx, Inc. | "EpicentRx...announced that The American Society of Clinical Oncology (ASCO) has invited Dr. Anthony P. Conley, an MD Anderson Cancer Center (MDACC) Sarcoma Specialist and Lead PI, to give an oral presentation on the unprecedented clinical activity of AdAPT-001 plus an immune checkpoint inhibitor (ICI) in the ongoing Phase 2 open-label BETA PRIME clinical trial that has so far enrolled close to 70 patients....To date, no dose-limiting toxicities or AdAPT-001 related serious adverse events have occurred and only one immune related adverse event (irAE) has been reported. This lack of irAEs suggests that AdAPT-001 may prevent or attenuate ICI-mediated immune attack on normal tissues but not cancerous ones."

P2 data • Breast Cancer • Oncology • Sarcoma • Solid Tumor • Triple Negative Breast Cancer

Improved clinical outcomes in patients received treatment beyond tumor progression with AdAPT-001 +/- a checkpoint inhibitor (AACR 2024) - "AdAPT-001 mediated PsP and TBP may serve as markers of prolonged clinical benefit. Further validation in larger numbers of future patients is warranted."

Checkpoint inhibition • Clinical • Clinical data • Oncology • TGFB1

EpicentRx to Present Positive Phase 2a Clinical Data with its AdAPT-001 TGF-β Trap Program in Checkpoint Inhibitor Resistant Patients at the 2024 AACR Meeting (PRNewswire) - P2a/2b | N=140 | BETA-PRIME (NCT04673942) | Sponsor: EpicentRx, Inc. | "EpicentRx...announced that an abstract on its lead therapy, AdAPT-001, will be presented at the American Association for Cancer Research (AACR) Annual Meeting....Data from a Phase 1/2 clinical trial demonstrate that administration of AdAPT-001 successfully converted immunologically cold tumors, such as sarcomas and triple negative breast cancer, into immunologically hot tumors. Furthermore, AdAPT-001 administration also demonstrates reversion of established resistance to checkpoint inhibitors."

P2a data • Sarcoma • Triple Negative Breast Cancer

BETA-PRIME: A Study of AdAPT-001 in Subjects With Sarcoma and Refractory Solid Tumors (clinicaltrials.gov) - P2 | N=140 | Recruiting | Sponsor: EpicentRx, Inc. | Trial completion date: Mar 2025 ➔ Mar 2027 | Trial primary completion date: Mar 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • TGFB1

BETA-PRIME: A Study of AdAPT-001 in Subjects With Sarcoma and Refractory Solid Tumors (clinicaltrials.gov) - P2 | N=140 | Recruiting | Sponsor: EpicentRx, Inc. | Phase classification: P1/2 ➔ P2 | N=79 ➔ 140

Enrollment change • Phase classification • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • TGFB1

BETA prime: a first-in-man phase 1 study of AdAPT-001, an armed oncolytic adenovirus for solid tumors. (PubMed, Cancer Gene Ther) - "The recommended Phase 2 dose was 1.0 × 10 vp administered by intratumoral injection once every 2 weeks. Combination of AdAPT-001 with a checkpoint inhibition is enrolling."

Journal • Oncolytic virus • P1 data • Fibrosis • Oncology • Solid Tumor

BETA prime: a first-in-man phase 1 study of AdAPT-001, an armed oncolytic adenovirus for solid tumors (Nature, Cancer Gene Ther) - P1/2 | N=79 | BETA-PRIME (NCT04673942) | Sponsor: EpicentRx, Inc. | "Part 1 enrolled 9 patients with a 3 + 3 single dose-escalation safety run-in involving 2.5 × 1011, 5.0 × 1011, 1.0 × 1012 viral particles (vps). No dose-limiting toxicities or treatment-related serious adverse events (SAEs) were seen. In Part 2, a dose-expansion phase, 19 patients received AdAPT-001 at 1.0 × 1012 vps until disease progression according to Response Evaluation Criteria in Solid Tumors or RECIST 1.1. The overall responses to treatment included confirmed partial responses (3), durable stable disease ≥ 6 months (5), and progressive disease (13). AdAPT-001 is well tolerated. Evidence of an anti-tumor effect was seen in both injected and uninjected lesions. The recommended Phase 2 dose was 1.0 × 1012 vp administered by intratumoral injection once every 2 weeks."

P1 data • Solid Tumor

BETA prime: a first-in-man phase 1 study of AdAPT-001, an armed oncolytic adenovirus for solid tumors (Nature, Cancer Gene Ther) - P1/2 | N=79 | BETA-PRIME (NCT04673942) | Sponsor: EpicentRx, Inc. | "Part 1 enrolled 9 patients with a 3 + 3 single dose-escalation safety run-in involving 2.5 × 1011, 5.0 × 1011, 1.0 × 1012 viral particles (vps). No dose-limiting toxicities or treatment-related serious adverse events (SAEs) were seen. In Part 2, a dose-expansion phase, 19 patients received AdAPT-001 at 1.0 × 1012 vps until disease progression according to Response Evaluation Criteria in Solid Tumors or RECIST 1.1. The overall responses to treatment included confirmed partial responses (3), durable stable disease ≥ 6 months (5), and progressive disease (13). AdAPT-001 is well tolerated. Evidence of an anti-tumor effect was seen in both injected and uninjected lesions. The recommended Phase 2 dose was 1.0 × 1012 vp administered by intratumoral injection once every 2 weeks."

P1 data • Solid Tumor

AdAPT-001 in advanced soft-tissue sarcoma (BETA PRIME): a multicenter, open-label, phase 1 clinical trial (SITC 2023) - P1/2 | "Conclusions AdAPT-001 showed encouraging activity in patients with STS. Enrollment to the Phase 2 portion of the study in combination with a checkpoint inhibitor is ongoing."

Clinical • Late-breaking abstract • Metastases • P1 data • Chordoma • Leiomyosarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • TGFB1

BETA-PRIME: A First in Human Study of AdAPT-001 in Subjects With Refractory Solid Tumors (clinicaltrials.gov) - P1/2 | N=79 | Recruiting | Sponsor: EpicentRx, Inc. | Trial completion date: Mar 2024 ➔ Mar 2025 | Trial primary completion date: Mar 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Oncology • Solid Tumor

TGF-β: the apex predator of immune checkpoints. (PubMed, Future Oncol) - No abstract available

Journal • Immune Modulation • TGFB1

Data Management 101 for Drug Developers: A Peek Behind the Curtain. (PubMed, Clin Transl Sci) - "For added color and context, the review includes real-world examples with RRx-001, a new molecular entity (NME) in Phase 3 and with fast-track status in head and neck cancer, and AdAPT-001, an oncolytic adenovirus armed with a transforming growth factor-beta (TGF-β) trap in a Phase 1/2 clinical trial with which the authors, as employees of the biopharmaceutical company, EpicentRx, are closely involved. An alphabetized glossary of key terms and acronyms used throughout this manuscript is also included for easy reference (See Table 1)."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • TGFB1

EpicentRx Presents Updates on its Oncology Clinical Development Programs at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (PRNewswire) - "EpicentRx...presented clinical progress updates for two lead oncology treatment candidates, RRx-001 and AdAPT-001, at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting being held June 2-6, 2023, in Chicago, IL and virtually....The company presented study design details for the Phase 2b KEVLARx study of RRx-001, which received FDA Fast Track designation for the treatment of severe oral mucositis based on data from the previous Phase 2a PREVLAR study. The company also presented promising first-in-human data for its transforming growth factor beta (TGFβ) trap vector, AdAPT-001."

Clinical protocol • Oncology • Solid Tumor

Initial results from a first in human dose escalation trial of a novel immune stimulating oncolytic adenovirus, AdAPT-001TGF-ß Trap. (ASCO 2023) - P1/2 | "AdAPT-001 TGF-ß Trap is well tolerated and no dose limiting toxicities were observed with the single or multidosing protocol described. Evidence of an antitumor effect was seen. The recommended Phase 2 dose was 1.0 x 1012 VPs administered by intratumoral injection once every 2 weeks."

Oncolytic virus • P1 data • Fatigue • Fibrosis • Melanoma • Oncology • Respiratory Diseases • Sarcoma • Solid Tumor

Treatment of 4T1 breast cancer with liposome-encapsulated AdAPT-001, a TGF-beta trap encoded oncolytic adenovirus currently in a phase 1/2 anticancer trial (SABCS 2022) - "Accordingly, we demonstrate a significant increase (P value= 0.0029) in the expression of green fluorescent protein (GFP) in CAR-negative 4T1 cells infected with the encapsulated AdAPT-001 adenovirus but not the unencapsulated AdAPT-001 adenovirus. Additional in vivo studies using nanoparticle encapsulated adenoviral vectors including AdAPT-001 to treat breast cancer are underway for rapid translation to the clinic."

IO biomarker • Oncolytic virus • P1/2 data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2 • PGR • TGFB1

BETA-PRIME: A First in Human Study of AdAPT-001 in Subjects With Refractory Solid Tumors (clinicaltrials.gov) - P1/2 | N=79 | Recruiting | Sponsor: EpicentRx, Inc. | Phase classification: P1 ➔ P1/2 | N=40 ➔ 79 | Trial completion date: Jun 2023 ➔ Mar 2024 | Trial primary completion date: Dec 2022 ➔ Mar 2023

Enrollment change • Phase classification • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

AdAPT-001, an oncolytic adenovirus armed with a TGF-β trap, overcomes in vivo resistance to PD-L1-immunotherapy. (PubMed, Am J Cancer Res) - P1 | "In this paper we evaluated combination therapy with a Phase 1 oncolytic adenovirus called AdAPT-001, armed with a TGF-β "trap" that binds to and neutralizes the immunosuppressive cytokine, TGF-β, and a checkpoint inhibitor, anti-PD-L1, in PD-L1 resistant tumors. The study, which was performed in an immunocompetent syngeneic ADS-12 mouse model, demonstrated that the combination of AdAPT-001 with PD-L1 blockade reversed PD-L1 resistance, potentially representing a future paradigm shift for patients that are primarily or secondarily resistant to checkpoint inhibitors."

Journal • Oncolytic virus • Preclinical • Bladder Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hematological Malignancies • Hodgkin Lymphoma • Lung Cancer • Lymphoma • Melanoma • Merkel Cell Carcinoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • CTLA4 • TGFB1