AVA6000 for Cancer

Recruiting at 8 trial locations

Overseen By Avacta Life Sciences

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Avacta Life Sciences Ltd

Must not be taking: Trastuzumab, Anthracyclines, QT prolonging drugs

Disqualifiers: CNS metastases, Other malignancy, Cardiovascular, others

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

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

Compensation: Varies

Number of Visits: 14

158 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer treatment called AVA6000, a FAP-activated doxorubicin prodrug, for individuals with certain advanced or metastatic solid tumors, such as breast, ovarian, or salivary gland cancer. Researchers aim to assess the safety of AVA6000 and determine the optimal dose. The trial includes different parts to test varying doses and observe the body's response. Eligible participants have confirmed advanced cancer that standard treatments have not helped or can no longer treat. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on certain medications like trastuzumab or have conditions that require specific treatments, you may need to discuss this with the trial team.

Is there any evidence suggesting that AVA6000 is likely to be safe for humans?

Research has shown that AVA6000 is generally safer than traditional doxorubicin, a common cancer drug. Patients typically tolerate AVA6000 well. In studies, AVA6000 targets cancer cells more precisely, potentially leading to fewer side effects. Although this information is preliminary, it suggests that AVA6000 could be safer for patients than some current treatments. However, as this is the first time AVA6000 is being tested in humans, researchers are still learning about its complete safety profile. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

AVA6000 is unique because it is designed to be a precision-targeted chemotherapy, aiming to reduce the side effects commonly associated with traditional chemotherapy drugs like doxorubicin. Unlike standard treatments that affect both cancerous and healthy cells, AVA6000 activates doxorubicin specifically within the tumor environment, potentially reducing damage to healthy tissues. Researchers are excited about AVA6000 because this targeting mechanism could lead to more effective cancer treatment with fewer harmful side effects, making it a promising alternative to current options.

What evidence suggests that AVA6000 might be an effective treatment for cancer?

Research has shown that AVA6000, the investigational treatment in this trial, may effectively treat certain cancers. Studies have found that it can deliver high doses of doxorubicin, a common chemotherapy drug, directly to tumors with high FAP activity. This approach attacks the cancer more effectively while protecting healthy tissues. Initial results indicated that some patients with salivary gland cancer experienced tumor shrinkage. There is also evidence of minor tumor shrinkage in other types of FAP-positive tumors. This targeted method could lead to fewer side effects compared to traditional chemotherapy. Participants in this trial will receive AVA6000 in different dosing schedules to evaluate its safety and effectiveness. ^{2 4 5 6 7}

Who Is on the Research Team?

Chris Twelves, MD

Principal Investigator

St James's University Hospital, Leeds, UK

Are You a Good Fit for This Trial?

This trial is for adults over 18 with certain advanced or metastatic solid tumors (like breast, ovarian, bladder cancer) that have not responded to standard treatments. Participants must be in good physical condition with a life expectancy of more than 12 weeks and have recovered from previous treatments' side effects.

Inclusion Criteria

Neutrophil count of ≥1.5× 10^9 cells/L

My cancer has returned or worsened after standard treatment, or I cannot tolerate the standard treatment.

Willing and able to give written informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of AVA6000 to evaluate safety, tolerability, and determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D).

Up to 28 days per cycle

Visits every 14 or 21 days depending on schedule

Dose Expansion

Participants receive AVA6000 at the recommended dose for expansion to further evaluate safety and efficacy.

Until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 30 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• AVA6000

Trial Overview AVA6000, a new drug given through the vein, is being tested on patients with FAP-positive tumors. The study has two parts: first finding the right dose and then seeing how well it works at that dose in more people.

How Is the Trial Designed?

Group I: AVA6000 Phase 1b Dose Expansion Experimental Treatment 1 Intervention

Patients in this arm will receive AVA6000 at the recommended dose for expansion, until disease progression, unacceptable toxicities, withdrawal from treatment for other reasons, reaching maximum lifetime cumulative exposure to doxorubicin (or other anthracyclines), or death, whichever occurs first.

Group II: AVA6000 Phase 1a Dose Escalation Q3W Experimental Treatment 1 Intervention

Patients in this arm will receive escalating doses of AVA6000 following a 3+3 design, Q3W until disease progression, unacceptable toxicities, withdrawal from treatment for other reasons, reaching maximum lifetime cumulative exposure to doxorubicin (or other anthracyclines), or death, whichever occurs first.

Group III: AVA6000 Phase 1a Dose Escalation Q2W Experimental Treatment 1 Intervention

Patients in this arm will receive escalating doses of AVA6000 following a 3+3 design, Q2W until disease progression, unacceptable toxicities, withdrawal from treatment for other reasons, reaching maximum lifetime cumulative exposure to doxorubicin (or other anthracyclines), or death, whichever occurs first.

AVA6000 is already approved in United States for the following indications:

Approved in United States as AVA6000 for:

• Soft tissue sarcoma (Orphan Drug Designation)

Who Is Running the Clinical Trial?

Avacta Life Sciences Ltd

Lead Sponsor

Trials

1

Recruited

160+

Published Research Related to This Trial

The FAPα-targeting prodrug of Doxorubicin (FTPD) effectively releases the drug in the presence of FAPα, demonstrating its potential for targeted tumor therapy, particularly in FAPα-positive tumors like the 4T1 model.

FTPD shows similar antitumor efficacy to free Doxorubicin in mice but with significantly reduced cardiotoxicity, indicating a safer delivery method for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the tumor targeting of a FAPα-based doxorubicin prodrug. Huang, S., Fang, R., Xu, J., et al.[2021]

In a study involving 9 patients with advanced solid tumors, 90Y-FAPI-46 radioligand therapy was found to be well tolerated, with a low incidence of serious adverse events, indicating its safety for use in heavily pretreated patients.

The therapy demonstrated sufficient tumor uptake in 78% of patients and showed signs of tumor response in 50%, suggesting potential efficacy, although further research is needed to confirm these findings in larger groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Clinical Experience with 90Y-FAPI-46 Radioligand Therapy for Advanced-Stage Solid Tumors: A Case Series of 9 Patients. Ferdinandus, J., Costa, PF., Kessler, L., et al.[2022]

The newly synthesized prodrug (+)-FDI-CBIM, which binds to human albumin, allows for over three times the dosage to be administered compared to the free drug, enhancing its potential for treatment.

In animal models, this prodrug demonstrated significantly improved antitumor efficacy against both syngeneic tumors and human ovarian xenografts, suggesting that forming drug-albumin conjugates could be a promising strategy for enhancing cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and antitumor activity evaluations of albumin-binding prodrugs of CC-1065 analog. Wang, Y., Jiang, J., Jiang, X., et al.[2019]

The study developed a doxorubicin prodrug conjugate linked to a monoclonal antibody targeting the insulin-like growth factor-1 receptor, which is overexpressed in many tumors, allowing for selective binding and accumulation in cancer cells.

This approach resulted in over 200-fold improved therapeutic index and reduced tumor load without systemic toxicity, effectively bypassing resistance mechanisms like p-glycoprotein efflux, making it a promising strategy for more effective cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prodrug chemotherapeutics bypass p-glycoprotein resistance and kill tumors in vivo with high efficacy and target-dependent selectivity. Guillemard, V., Uri Saragovi, H.[2018]

PhAc-ALGP-Dox is a novel targeted prodrug designed to reduce the toxic effects of doxorubicin, showing improved safety profiles in normal tissues and significantly higher tolerability in preclinical models, with a 10-fold increase compared to standard doxorubicin.

In preclinical studies, PhAc-ALGP-Dox demonstrated impressive efficacy, achieving 63% to 96% tumor growth inhibition and an 8-fold improvement in effectiveness in patient-derived xenograft models, while also reducing metastatic burden and improving survival rates by 30%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PhAc-ALGP-Dox, a Novel Anticancer Prodrug with Targeted Activation and Improved Therapeutic Index. Casazza, A., Van Helleputte, L., Van Renterghem, B., et al.[2023]

The study developed new drug conjugates, FA-FU-DOX, which enhance the selectivity and effectiveness of doxorubicin (DOX) in targeting cancer cells while potentially reducing its cardiotoxic side effects.

These conjugates showed improved drug release rates in acidic conditions (pH 5.9), increased cellular uptake in liver cancer cells, and greater cytotoxicity against those cancer cells compared to standard DOX, indicating a promising strategy for safer cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis, Characterization, Cellular Uptake, and In Vitro Anticancer Activity of Fullerenol-Doxorubicin Conjugates. Xu, B., Yuan, L., Hu, Y., et al.[2021]

Doxorubicin conjugates and prodrugs are being developed to selectively activate the drug at tumor sites, aiming to reduce severe side effects seen in previous treatments like cBR96-Dox, which was discontinued due to toxicity.

New strategies, including antibody-directed enzyme prodrug therapy (ADEPT) and receptor-mediated targeting, are being explored to enhance the delivery and effectiveness of doxorubicin, with some conjugates already reaching clinical levels and showing promise in treating solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Doxorubicin conjugates for selective delivery to tumors. Florent, JC., Monneret, C.[2013]

The study presents a novel dual-mechanism targeted bioorthogonal prodrug therapy that enhances the delivery and activation of cancer treatments, specifically doxorubicin, by using two independent targeting strategies to improve efficacy and safety.

By utilizing the body's natural albumin transport system and enzyme-instructed self-assembly, the therapy allows for controlled activation of the prodrug at the tumor site, potentially reducing side effects and improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Dual-Mechanism Targeted Bioorthogonal Prodrug Therapy. Yao, Q., Lin, F., Lu, C., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04969835

NCT04969835 | A Study Evaluating the Safety, ... This is a first-in-human (FIH), Phase 1 open-label, multicentre dose escalation study investigating AVA6000 monotherapy administered intravenously in ...

2. avacta.com avacta.com/avacta-therapeutics-presents-data-from-lead-precision-candidate-fap-dox-ava6000-at-the-2025-aacr-annual-meeting/

CISION® Candidate FAP-Dox (AVA6000) at the 2025 ... Compelling Phase 1 safety and efficacy data for FAP-Dox (AVA6000) with preliminary evidence of efficacy in salivary gland cancers and no ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02231-2/fulltext

646P A phase I trial of AVA6000, a fibroblast activation ... Two PR (RECISTv.1.1) and 3 minor responses (-10 to -29%) were observed in 5 pts with FAPhigh tumor types including salivary gland cancer and soft ...

4. onclive.com onclive.com/view/ava6000-generates-early-efficacy-is-safe-in-advanced-salivary-gland-cancers

AVA6000 Generates Early Efficacy, Is Safe in Advanced ... AVA6000 showed early efficacy and safety signals in previously treated, locally advanced or metastatic salivary gland cancers.

5. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/CT188/742634/Abstract-CT188-A-Phase-I-trial-of-AVA6000-a

Abstract CT188: A Phase I trial of AVA6000, a Fibroblast ... AVA6000 delivers high concentration of doxorubicin to the TME relative to plasma which results in antitumor activity in tumors with high FAP activity.

6. avacta.com avacta.com/avacta-announces-promising-early-efficacy-and-safety-data-for-ava6000-in-the-phase-1a-dose-escalation-and-ongoing-enrollment-in-the-phase-1b-expansion-cohorts/

Avacta Announces Promising Early Efficacy and Safety ... As of the most recent data cut-off, the favorable safety profile continues to be observed when compared with conventional dose doxorubicin, ...

7. fredhutch.org fredhutch.org/en/research/clinical-trials/trial-details.fh_trial_id_14487.a-study-evaluating-the-safety-pharmacokinetics-and-early-efficacy-of-ava6000-in-solid-tumours.html

Clinical Trial Details This open-label, First-into-Human (FIH) study will evaluate the safety, tolerability, pharmacokinetics (PK) and early efficacy of AVA6000, a FAP-activated pro- ...