Successful Completion of ALS-6000-101 Sixth Dose Escalation and Clinical Update

  • Excellent safety profile of AVA6000 continues to be observed in the sixth dose escalation cohort.
  • Significant reduction in tumour volume confirmed in a patient with soft tissue sarcoma.
  • Cohort 7 to be the final dose escalation cohort in the Phase 1a three weekly dosing study.
  • Revised regulatory strategy aims to achieve earlier commencement of pivotal Phase 2 study in soft tissue sarcoma in 2024.
  • Detailed Phase 1a data expected to be released in Q4 2023.

Avacta Group plc (AIM: AVCT), a life sciences company developing innovative, targeted oncology drugs and powerful diagnostics, today announces the successful completion of the sixth dose escalation cohort in the ALS-6000-101 dose escalation Phase 1 clinical trial to evaluate the safety and tolerability of AVA6000 and provides an update on clinical progress.

The data from the sixth cohort continue to show an excellent safety profile for AVA6000. Additionally, a tumour response (significant tumour volume reduction) has been confirmed in a patient with soft tissue sarcoma on the trial, and there are further indications of clinical activity in patients across other indications.

AVA6000 is a tumour targeted form of doxorubicin that has been chemically modified with Avacta’s pre|CISION™ platform, designed to reduce systemic side effects by targeting the release of the active chemotherapy to tumour tissue.

A total of 35 patients with a range of advanced and/or metastatic solid tumours have now been dosed at the clinical trial in sites in the UK and United States. AVA6000 continues to be well tolerated by patients in cohort 6 despite receiving 2.79 times the typical dose of doxorubicin. A clinically significant reduction in the toxicities usually associated with standard doxorubicin chemotherapy continues to  be observed. These data continue to demonstrate the potential to administer higher doses, more cycles of AVA6000, or more frequent dosing compared to doxorubicin.

On the basis of the very favourable safety profile of AVA6000, the Safety Data Monitoring Committee (SDMC) has recommended continuation to the seventh dose cohort at 385 mg/m2, which is equivalent to approximately 3.5 times the standard dose of doxorubicin.

The Company and its advisers have decided that Cohort 7 will be the final dose escalation cohort in the ALS-6000-101 Phase 1a safety study for three weekly dosing.

In addition to the excellent safety profile being observed for AVA6000, clear signs of efficacy have now been confirmed. One patient with soft tissue sarcoma has shown a significant reduction in tumour volume in response to the drug, with further signs of activity observed in patients with cancers not limited to soft tissue sarcoma.

In light of the positive data emerging from the ALS-6000-101 study the Company has adapted its clinical development strategy with the aim of bringing forward the start of a potentially pivotal phase 2 study in soft tissue sarcoma, subject to receiving the necessary regulatory approvals.

The excellent safety profile of AVA6000 should allow more frequent and/or higher dosing compared with the standard doxorubicin regimen which could in turn improve the outcome for patients. Therefore, in parallel with the completion of cohort 7, the Company intends to begin a short study to explore more frequent dosing (fortnightly) of AVA6000 as a first line treatment in patients with soft tissue sarcoma. The study is expected to begin in Q4 2023 subject to receipt of approval of a protocol amendment from the US Food & Drug Administration (FDA).

The study is designed to determine whether fortnightly or three weekly dosing should be the recommended Phase 2 dosing regimen, as well as potentially providing additional indications of activity in soft tissue sarcoma patients. The study will replace the much longer planned Phase 1b efficacy study, and is expected to allow the Company to bring forward the start of the potentially pivotal Phase 2 efficacy study into 2024.

The Company expects to publish detailed data from the ALS-6000-101 clinical study, including clinical and pharmacokinetic data, in the fourth quarter of 2023.

Dr Alastair Smith, Chief Executive of Avacta Group plc commented:

“I believe that we are on the verge of a paradigm shift in how chemotherapy is delivered to cancer patients. 

The safety and initial efficacy signals emerging from the data in the AVA6000 Phase 1 study are very encouraging indeed. The pre|CISIONTM platform is doing exactly what it was designed to do – target the release of active chemotherapy to the tumour tissue, sparing healthy tissues and improving the safety and tolerability of the drug whilst delivering potentially superior efficacy. 

I’m particularly pleased that, even at this early stage and in this patient group, we have a confirmed, significant response in a patient with soft tissue sarcoma, as well as other positive signals across a number of other patients. 

We’re now aiming to accelerate the clinical development of AVA6000 and begin the Phase 2 efficacy study earlier than originally planned. The Phase 2 trial will follow a short study to determine the safety and efficacy of fortnightly dosing to allow us to determine the recommended Phase 2 dosing regimen. 

I look forward very much to sharing the detailed data from the Phase 1a study in due course.”