AVA6000 / Avacta - LARVOL DELTA

Investigating fibroblast activation protein alpha (FAPα) as a therapeutic target for delivery of pre|CISION® cancer medicines: Expression, spatial localization and functional insights (AACR 2025) - "The potential of the pre|CISION® technology is highlighted by the promising clinical data from AVA6000, a pre|CISION® enabled Doxorubicin peptide drug conjugate...Avacta's preCISION® peptide-drug conjugates elicit bystander cell kill over a range of physiological FAP levels within these co-culture models. Combined, these analyses emphasize the significance of FAP as an important stromal target for focused delivery of targeted oncology therapeutics, and guide further development of the preCISION® pipeline."

Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • CAFs • FAP

Comparative pharmacokinetics and tumor activation of fibroblast activation protein (FAP)-enabled pre|CISION® peptide drug conjugates (AACR 2025) - "Two payloads are described using this platform: AVA6000 (doxorubicin [dox]; pre-clinical and clinical) and AVA6103 (exatecan, pre-clinical). In the Phase 1 trial, AVA6000 exhibits promising tumor-targeting characteristics with encouraging clinical activity and reduced systemic toxicities validating the tumor-specific FAP cleavage mode of action. These AVA6000 data along with the preclinical PK data with AVA6103 have informed the predictive modeling to support the clinical development of AVA6103 by optimizing the delivery of the exatecan payload."

PK/PD data • Oncology • Salivary Gland Cancer • Solid Tumor

AVA6000 (FAP-Dox) Clinical Highlights (Abstract #CT15, Apil 29, 2025) (GlobeNewswire) - P1a | N=158 | NCT04969835 | Sponsor: Avacta Life Sciences Ltd | "AVA6000 is a FAP-activated form of doxorubicin designed to reduce the systemic side effects of conventional chemotherapy. In the Phase 1a dose-escalation study, AVA6000 was well-tolerated across both every-three-week (Q3W) and every-two-week (Q2W) dosing regimens. No maximum tolerated dose (MTD) was reached despite dosing up to 385 mg/m² every three weeks....In patients with salivary gland cancers (SGC, n=11) treated at or above the dose level of 250 mg/m2, AVA6000 demonstrated multiple confirmed responses and a disease control rate of 91%....The full Phase 1a data across all patients (n=63), including a full assessment of the cardiac safety data with long-term follow-up are expected in the second half of 2025....Avacta continues to enroll patients in three Phase 1b expansion cohorts in salivary gland cancer, triple negative breast cancer and high-grade soft tissue sarcoma with data anticipated by the end of 2025."

P1 data • Salivary Gland Cancer • Soft Tissue Sarcoma • Triple Negative Breast Cancer

Avacta Therapeutics Announces Presentations at 2025 AACR Annual Meeting (GlobeNewswire) - "The poster presentations will feature data from the Company’s proprietary pre|CISION platform and pipeline of next generation peptide drug conjugates (PDCs), including AVA6000, a PDC consisting of doxorubicin conjugated with a peptide moiety that is specifically cleaved by FAP in the tumor microenvironment via a pharmacokinetics and clinical presentation, and preclinical pharmacology highlights for AVA6103, a PDC comprised of the pre|CISION peptide linked to exatecan. The third presentation will describe detailed analysis of the target fibroblast activation protein-alpha (FAPα), the protease that forms the basis of the pre|CISION platform."

Preclinical • Oncology

AVA6000 Generates Early Efficacy, Is Safe in Advanced Salivary Gland Cancers (OncLive) - "'We are very excited to move the development of AVA6000 to the next level to generate data that demonstrates clinically meaningful efficacy and durability of response in patients with previously treated salivary gland cancers,' Alan Ho, MD...stated in a news release. 'It is important to note the high degree of unmet need in this disease where few agents have shown efficacy. I am happy to participate in the trials of AVA6000 in this disease setting in the future.'"

Media quote

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 (Firstwordpharma Press Release) - "Alan Ho, MD...commented: 'We are very excited to move the development of AVA6000 to the next level to generate data that demonstrates clinically meaningful efficacy and durability of response in patients with previously treated salivary gland cancers. It is important to note the high degree of unmet need in this disease where few agents have shown efficacy. I am happy to participate in the trials of AVA6000 in this disease setting going forward.'"

Media quote

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 (GlobeNewswire) - P1 | N=158 | NCT04969835 | Sponsor: Avacta Life Sciences Ltd | "Avacta Therapeutics...is pleased to announce that the lead program of the Company, AVA6000...has completed the Phase 1a dose escalation with encouraging PFS data in patients with salivary gland cancers. The Company has initiated enrollment in the Phase 1b expansion cohorts with multiple patients treated....Among these 11 patients, one patient experienced a confirmed partial response as best response (greater than -30% reduction in tumor diameters by RECIST criteria), four patients had minor responses (-10 to -29% reduction by RECIST criteria), and only one patient had disease progression for a disease control rate of 91%....The Company anticipates providing a further update from the Phase 1a dose escalation data in 2Q 2025 and Phase 1b dose expansion cohort data at the end of 2025. The full Phase 1a data will be presented in 2H 2025, including a full assessment of the cardiac safety data with long-term follow up."

P1 data • Trial status • Salivary Gland Cancer • Soft Tissue Sarcoma • Triple Negative Breast Cancer

Avacta Announces Positive New Data from the AVA6000 Phase 1 trial Demonstrating Clinically Meaningful Tumor Shrinkage in Patients with Salivary Gland Cancers (GlobeNewswire) - P1a | N=158 | NCT04969835 | Spnonsor: Avacta Life Sciences Ltd | "The data demonstrates robust and meaningful tumor shrinkage in patients with salivary gland cancers, a disease with no standard therapy defined in the metastatic setting...Among 10 patients treated at the dose of 250 mg/m2 and above, five patients demonstrate tumor shrinkage (one partial and four minor responses); Six of these 10 patients are continuing treatment and an additional two patients, who have reached maximum cycles, are still in follow up for progression free survival; The safety profile of AVA6000 continues to demonstrate a robust reduction in severe hematologic and cardiac toxicities that are associated with conventional dose doxorubicin."

P1 data • Salivary Gland Cancer

ALS-6000-101: A Study Evaluating the Safety, Pharmacokinetics and Early Efficacy of AVA6000 in Solid Tumours (clinicaltrials.gov) - P1 | N=158 | Recruiting | Sponsor: Avacta Life Sciences Ltd | N=80 ➔ 158 | Trial completion date: Jun 2023 ➔ Aug 2026 | Trial primary completion date: May 2023 ➔ Mar 2026

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Biliary Tract Cancer • Breast Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Salivary Gland Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

A phase I trial of AVA6000, a fibroblast activation protein (FAP)-released, tumor microenvironment (TME)-targeted doxorubicin peptide drug conjugate in patients with FAP-positive solid tumors (ESMO 2024) - P1 | "AVA6000 delivers high concentration of free dox to the TME relative to plasma, resulting in antitumor activity in FAPhigh tumor types with reduced systemic dox exposure, resulting in lower toxicity versus conventional dox."

Biomarker • Clinical • P1 data • Tumor microenvironment • Oncology • Salivary Gland Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • FAP

Avacta Reports Updated Phase 1 Clinical Data of AVA6000 at the European Society for Medical Oncology (ESMO) Congress Demonstrating Multiple Ongoing, Durable Responses in Solid Tumors (GlobeNewswire) - P1 | N=80 | NCT04969835 | Sponsor: Avacta Life Sciences Ltd | "Patients had a median of two prior systemic cancer therapies (range 0-7) with 65% including cytotoxic exposure. Reduction in the sum of longest diameters (SLD) is used to measure response per RECIST 1.1 with partial responses of >30% reduction and minor responses of between >10% and <30% reduction. Among patients with FAPhigh cancers (n=23), three partial responses and four minor responses were observed...Among patients with FAPmid cancers (n=26), two minor responses were observed...Treatment with AVA6000 continues to be well-tolerated with the addition of the Q2W dosing regimen (Arm 2) with a favorable safety profile and reduction in severe and mild-to-moderate treatment-emergent toxicities as compared with conventional dose doxorubicin. A maximum tolerated dose has not been identified in either arm of the trial...No new dose limiting toxicities were observed and neither arm has determined an MTD."

P1 data • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Avacta to present updated clinical data on AVA6000 at the European Society for Medical Oncology (ESMO) Congress (GlobeNewswire) - "Avacta Group plc...announces that the company will present updated data from the Phase 1a trial of AVA6000 at the 2024 European Society for Medical Oncology (ESMO) Congress....The poster presentation will be based on an updated data cut from the Phase 1a trial of AVA6000 in patients with Fibroblast Activation Protein (FAP)-positive solid tumours. AVA6000 is a peptide drug conjugate consisting of doxorubicin conjugated with a peptide moiety that is specifically cleaved by FAP in the tumour microenvironment."

P1 data • Solid Tumor

Avacta reports further progress in chemotherapy trial (Sharecast) - "Avacta Group announced the successful completion of the first cohort and the start of dosing for three patients in the second cohort of the second arm in its phase one trial of AVA6000, a peptide drug conjugate form of doxorubicin chemotherapy, on Thursday....The first cohort in the second arm was completed without any adverse safety signals, and the second cohort had started dosing, with three patients already treated....Avacta said it remained on track to achieve its goals for the second half of 2024, including the start of the dose expansion phase 1b efficacy study and the presentation of further data from the AVA6000 trial."

New P1 trial • Trial status • Biliary Tract Cancer • Bladder Cancer • Breast Cancer • Colorectal Cancer • Gastroesophageal Cancer • Head and Neck Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Soft Tissue Sarcoma • Solid Tumor

A Phase I trial of AVA6000, a Fibroblast Activation Protein (FAP)-released and tumor microenvironment (TME)-targeted doxorubicin peptide drug conjugate in patients with FAP-positive solid tumors (AACR 2024) - "AVA6000 delivers high concentration of doxorubicin to the TME relative to plasma which results in antitumor activity in tumors with high FAP activity. A q2w dose escalation arm is ongoing."

Biomarker • Clinical • P1 data • Tumor microenvironment • Angiosarcoma • Biliary Tract Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma • FAP

Avacta Group - AVA6000 Abstract Release by AACR and Full Presentation Update (GlobeNewswire) - "Avacta Group plc...announces that the abstract of the poster to be presented at the American Association of Cancer Research ('AACR') Annual Meeting in San Diego, California on Tuesday 9 April has now been released by AACR. The poster presentation will be based on data from the Phase 1a trial of AVA6000, a peptide drug conjugate consisting of doxorubicin conjugated with a peptide moiety that is specifically cleaved by fibroblast activation protein (FAP) in the tumor microenvironment."

P1 data • Solid Tumor

This needs to be highlighted again. Sujana Movva has been the Co-Investigator for AVA6000 at MSKCC. Speciality - Sarcoma. Late last year a second Co-Investigator was added to the trial. Alan Ho. Speciality - Head & Neck. #AVCT

Updated Results from Single-Agent Phase 1 Clinical Trial of Peptide Drug Conjugate, AVA6000 to be Presented in a Poster at the American Association of Cancer Research (AACR) Annual Meeting on April 9, 2024 (GlobeNewswire) - "Avacta Group plc...today announces updated clinical data from the First-in-Human Phase 1 trial of the peptide drug conjugate, AVA6000 will be presented at the 2024 American Association for Cancer Research (AACR) Annual Meeting, taking place in San Diego, California from 5-10 April 2024."

P1 data • Oncology • Solid Tumor

ALS-6000-101 Phase 1a Three-Weekly Dose Escalation Safety Study Data (GlobeNewswire) - P1 | N=80 | NCT04969835 | Sponsor: Avacta Life Sciences Ltd | "Avacta Group plc...is pleased to provide detailed pre-clinical, clinical and pharmacokinetic data from the Phase 1a dose escalation study of its lead pre|CISION^TM programme, AVA6000, a tumour activated form of doxorubicin....Preliminary results in the Phase 1a trial demonstrate activity of AVA6000 in patients with tumours with high FAP activity, validating the mechanism of action of AVA6000. For example, a 59-year-old male patient with Undifferentiated Pleomorphic Sarcoma (UPS) has shown a reduction in tumour volume of 65% with a duration of response >6 months and ongoing....Given the favourable safety data from the three-weekly dosing study, a fortnightly dosing study, which is now screening patients with high FAP levels in the United States, will assist in optimising the schedule and dose for a potentially pivotal Phase 2 study in 2024."

P1 data • Soft Tissue Sarcoma • Solid Tumor

Successful Completion of Sixth Dose Escalation (London South East) - P1 | N=80 | NCT04969835 | Sponsor: Avacta Life Sciences Ltd | "Avacta Group plc...announces the successful completion of the sixth dose escalation cohort in the ALS-6000-101 dose escalation Phase 1 clinical trial....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....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....Cohort 7 will be the final dose escalation cohort in the ALS-6000-101 Phase 1a safety study....The Company expects to publish detailed data from the ALS-6000-101 clinical study in the fourth quarter of 2023."

P1 data • Trial status • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Successful Completion of Sixth Dose Escalation (London South East) - "...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."

New P2 trial • New trial • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Avacta Announces Successful Completion of Fifth Dose Escalation in AVA6000 Phase 1 Clinical Study (Businesswire) - P1 | N=80 | ALS-6000-101 (NCT04969835) | Sponsor: Avacta | "Avacta Group plc...announces that the fifth dose escalation cohort in the ALS-6000-101 dose escalation Phase 1 clinical trial to evaluate the safety and tolerability of AVA6000 has been completed successfully. The data continue to show a very favourable safety profile for the tumour targeted chemotherapy and several patients in cohort 5 and earlier cohorts remain on treatment as their disease has not progressed....The emerging positive safety and pharmacokinetic data from the study support the potential clinical differentiation of AVA6000 over doxorubicin."

P1 data • Trial status • Oncology • Solid Tumor

First Patient Dosed in the US in Avacta’s AVA6000 Phase 1 Clinical Study (Businesswire) - "Avacta Group plc...announces that the first patient has been dosed in the US under its Investigational New Drug (IND) Application in Avacta’s phase 1 multi-centre trial evaluating the safety and tolerability of AVA6000....The first patient in the US has been dosed in the dose-escalation study in patients with locally advanced or metastatic selected solid tumours, known to be FAP-positive, at the Memorial Sloan Kettering Cancer Center in New York."

Trial status • Oncology • Solid Tumor

"Avactas AVA6000 doesn't need phase 3, it's not a new drug" (@ZosoGraffiti)

P3 data

Avacta Announces First Patient Dosed in Fifth Cohort of AVA6000 Phase Ia Dose Escalation Study (Businesswire) - "Avacta Group plc...announces that the first patient has been dosed in the fifth cohort of the first-in-human phase I trial (ALS-6000-101) of AVA6000. This follows the approval of an amended clinical trial protocol by the Medical and Healthcare Products Regulatory Agency (MHRA) to allow for higher levels of dosing....Avacta’s Safety Data Monitoring Committee (SDMC), comprised of clinicians currently recruiting patients, has recommended that the phase Ia dose escalation clinical trial continues to a fifth dose cohort at 250mg/m2, following the favourable safety profile of AVA6000 generated in the study to date. Escalation to this level of dosing falls outside of the original clinical trial protocol, and therefore the protocol required amendment and approval by the MHRA, which has now been completed. This continued dose escalation is aimed at identifying a maximum tolerated dose (MTD) necessary to inform the dosing levels for the phase 1b and future studies."

DSMB • Trial status • Bladder Cancer • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Soft Tissue Sarcoma • Solid Tumor

Avacta Opens First Two US Clinical Investigator Sites for AVA6000 Phase 1 Clinical Study (Businesswire) - "Avacta Group plc...announces the opening on 5 April 2023 of the first two clinical investigator sites for the phase 1 clinical trial of AVA6000 under its US Investigational New Drug (IND) Application. The two sites, Memorial Sloan Kettering Cancer Center (MSK) in New York and Fred Hutch Cancer Center in Seattle, are now open for patient enrolment to ALS-6000-101."

Trial status • Bladder Cancer • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Thoracic Cancer