AdAPT-001 for Cancer

(BETA-PRIME Trial)

Recruiting at 5 trial locations

Overseen By Jeannie Williams

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: EpicentRx, Inc.

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Active infection, HIV, Hepatitis, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 25

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of AdAPT-001, an oncolytic virus injected directly into solid tumors. Researchers aim to determine whether AdAPT-001 works better alone or when combined with a checkpoint inhibitor, a drug that helps the immune system fight cancer. The trial seeks participants with advanced solid tumors, such as sarcoma, who have exhausted all standard treatments and have tumors accessible for injection. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important cancer research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have chemotherapy or immunotherapy within 14 days of starting the study treatment. Hormonal therapies and certain other treatments are allowed.

Is there any evidence suggesting that AdAPT-001 is likely to be safe for humans?

Research has shown that AdAPT-001 has been tested for safety and tolerability. In one study, most participants tolerated AdAPT-001 well, experiencing mild side effects such as fatigue or fever. Serious side effects were rare.

AdAPT-001 has also been tested with checkpoint inhibitors, a type of cancer treatment. This combination showed promise in treating advanced cancers, with safety similar to using AdAPT-001 alone. No unexpected severe side effects were reported.

AdAPT-001 has received FDA Fast Track Designation, indicating potential in early studies, which often include safety information. However, further studies are necessary to fully understand the safety and effectiveness of AdAPT-001. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about AdAPT-001 because it offers a novel approach to treating advanced solid tumors, including sarcoma. Unlike traditional treatments that often rely on chemotherapy or radiation, AdAPT-001 uses a unique mechanism involving an engineered adenovirus to target and kill cancer cells directly. Additionally, when combined with a checkpoint inhibitor, it may enhance the immune system's ability to recognize and attack tumors, potentially improving outcomes for patients. This dual-action strategy could provide a more effective and targeted treatment option compared to existing therapies.

What evidence suggests that AdAPT-001 might be an effective treatment for cancer?

Research has shown that AdAPT-001 may help treat advanced solid tumors. In previous studies, about 62.5% of patients benefited, with their cancer either shrinking or ceasing to grow. In this trial, participants will receive AdAPT-001 either alone or with checkpoint inhibitors. AdAPT-001 enhances the immune system's ability to attack tumors, especially when combined with checkpoint inhibitors, which improve T-cells' targeting of cancer cells. Additionally, patients in these studies demonstrated improved progression-free survival rates, meaning their disease did not worsen for a period. These findings suggest that AdAPT-001 could be a promising option for certain types of cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Bryan Oronsky, MD PhD

Principal Investigator

EpicentRx, Inc.

Are You a Good Fit for This Trial?

Adults with advanced solid tumors that have failed conventional treatments can join this trial. They must have good liver, kidney, and blood health, not be pregnant or breastfeeding, use contraception if of childbearing potential, and understand the study's risks. Excluded are those with HIV, active hepatitis or autoimmune diseases requiring steroids, recent chemotherapy or immunotherapy (within 14 days), uncontrolled infections including COVID-19 within 14 days.

Inclusion Criteria

Subject has an INR < 1.5

I have an advanced cancer that has been confirmed by tests, and it's accessible for treatment.

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

Exclusion Criteria

You have a serious medical condition or an untreated health problem that could interfere with the study.

I have not had adenoviral therapy except for vaccines, and it's been 7 days since my last vaccine.

I haven't had chemotherapy or immunotherapy in the last 14 days, but I may be on hormonal therapy or treatments for bone health.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation Safety Run-In

Participants receive a single injection of AdAPT-001 to determine the highest safe and tolerable dose

28 days

1 visit (in-person)

Dose Expansion Single-Agent

Participants receive injections of AdAPT-001 on Days 1 and 15 of 28-day cycles

6 months

12 visits (in-person)

Expansion

Participants receive AdAPT-001 with or without a checkpoint inhibitor on Days 1 and 15 of 28-day cycles

6 months

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AdAPT-001

Trial Overview The trial is testing AdAPT-001—an oncolytic virus injected into tumors—to determine its highest safe dose for future cancer treatment. It's a first-in-human study to see if it could help treat various cancers by injecting directly into the tumor sites.

How Is the Trial Designed?

Group I: Phase 2 (Enrollment Open) Experimental Treatment 2 Interventions

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 II: PART 3: Expansion (Enrollment Completed) Experimental Treatment 2 Interventions

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 III: PART 2: Dose Expansion Single-Agent (Enrollment Completed) Experimental Treatment 1 Intervention

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 IV: PART 1: Dose Escalation Safety Run-In (Enrollment Completed) Experimental Treatment 1 Intervention

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

AdAPT-001 is already approved in United States for the following indications:

Approved in United States as AdAPT-001 for:

• Recurrent or refractory advanced or metastatic soft tissue sarcoma (STS)

Who Is Running the Clinical Trial?

EpicentRx, Inc.

Lead Sponsor

Trials

16

Recruited

1,000+

Published Research Related to This Trial

Identifying key driver mutations in cancer and their effects on molecular mechanisms is crucial for developing personalized medicine strategies, but many biomarkers lack independent validation.

Advancements in '-omic' technologies and large-scale projects like the International Cancer Genome Consortium are essential for cataloging cancer aberrations, which will aid in discovering biomarkers for therapy responsiveness and developing new treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical strategies to define predictive biomarkers for therapeutically relevant cancer subtypes. Pajic, M., Scarlett, CJ., Chang, DK., et al.[2021]

Research has shown that tumor antigens can trigger immune responses in cancer patients, but these responses often fail to stop tumor progression, highlighting the need for enhanced immunization strategies.

Early clinical trials of cancer vaccines have shown some clinical benefits, but challenges remain in identifying effective antigens, defining the immune responses needed, and selecting suitable delivery systems for the vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer vaccines and immunotherapies: emerging perspectives. Henderson, RA., Mossman, S., Nairn, N., et al.[2005]

A new screening method using phage display successfully identified specific peptides recognized by antibodies from prostate cancer patients, highlighting a consensus motif linked to cancer progression.

The presence of antibodies against this peptide motif was associated with shorter survival rates and the development of metastatic disease, suggesting its potential as a molecular marker for targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fingerprinting the circulating repertoire of antibodies from cancer patients. Mintz, PJ., Kim, J., Do, KA., et al.[2023]

Disease-related antigens are crucial in clinical settings for cancer screening, monitoring therapy responses, and serving as therapeutic targets, highlighting their importance in cancer management.

Protein microarrays have been effectively utilized to identify these antigens across various diseases, including cancer, by comparing immune responses from patient samples to those of healthy controls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum profiling using protein microarrays to identify disease related antigens. Sharon, D., Snyder, M.[2021]

The MATCH-R trial successfully obtained tumor biopsies from 303 out of 333 patients (91%), allowing for extensive molecular profiling to understand resistance mechanisms in cancer treatments.

Out of the biopsies, 278 samples (83%) were suitable for high-throughput sequencing, leading to the establishment of 54 patient-derived xenograft models, demonstrating the feasibility of using these models to inform future treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and first reports of the MATCH-R repeated biopsy trial at Gustave Roussy. Recondo, G., Mahjoubi, L., Maillard, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04673942

NCT04673942 | A Study of AdAPT-001 in Subjects With ... To evaluate the efficacy of the two-arm dose regimens of AdAPT-001 in subjects with advanced solid tumors that have progressed after treatment with standard ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2618

Effect of AdAPT-001 on checkpoint inhibitor resistance in ... Clinical data demonstrate that AdAPT-001 reverses the tumor immune evasion phenotype and improves the efficacy of immune checkpoint therapy, ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11016464/

BETA prime: a first-in-man phase 1 study of AdAPT-001 ... The overall responses to treatment included confirmed partial responses (3), durable stable disease ≥ 6 months (5), and progressive disease (13) ...

4. onclive.com onclive.com/view/adapt-001-gets-fda-fast-track-designation-in-recurrent-refractory-soft-tissue-sarcoma

AdAPT-001 Gets FDA Fast Track Designation in Recurrent ... The 6-month progression-free survival (PFS) rates among evaluable patients (n = 13) were 38% per RECIST 1.1 criteria and 54% per clinical ...

5. jitc.bmj.com jitc.bmj.com/content/12/10/e009613

TGF-β trap of AdAPT-001 turns up the heat on tumors and ... In addition, a 62.5% clinical benefit rate consisting of complete or partial responses or stable disease was observed. A few of the clinical ...

6. nature.com nature.com/articles/s41417-023-00720-0

BETA prime: a first-in-man phase 1 study of AdAPT-001 ... The aim or purpose of this phase 1 study was to assess the safety and tolerability and, secondarily, the efficacy of AdAPT-001 after single ...

7. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A760

663 AdAPT-001, a first-in-class 2-in-1 TGF-beta inhibitor ... Conclusions AdAPT-001 not only sensitizes ICI-resistant tumors to ICI therapy, leading to durable complete and partial responses, but also may ...