narmafotinib (AMP945) / Amplia Therap, Cancer Therapeutics CRC - LARVOL DELTA

ACCENT TRIAL DATA DEMONSTRATES THAT NARMAFOTINIB + CHEMOTHERAPY COMBINATION SUPERIOR TO CHEMOTHERAPY ALONE (Amplia Therapeutics Press Release) - P1b/2a | N=62 | ACCENT (NCT05355298) | Sponsor: Amplia Therapeutics Limited | "Fifteen (15) confirmed partial responses. (PRs) have now been recorded in the trial, a level of response sufficient to demonstrate that the combination of narmafotinib and chemotherapy is superior to chemotherapy alone. A confirmed partial response is a formal designation of response where tumour shrinkage >30% is recorded and sustained for two (2) or more months and where no new cancerous lesions have been detected. As pancreatic cancer is highly aggressive it is extremely rare for patients to achieve a complete response (CR)....At the outset of the study a statistical analysis was performed which identified that a patient cohort of 50 patients would be sufficient to allow the efficacy of our combination to be ascertained with reasonable confidence if 15 or more responders (confirmed PR or CR) were recorded....Phase 2a ACCENT trial is fully recruited with top-line data expected in mid Q3 2025."

P1/2 data • Pancreatic Cancer

Narmafotinib (AMP945) in combination with gemcitabine and nab paclitaxel in first-line patients with advanced pancreatic cancer (ACCENT trial) a phase 2a study: Interim analysis (AACR 2025) - P1/2 | "Preliminary Part B analysis on the initial 26 patients showed narmafotinib to be safe and well-tolerated with promising signs of efficacy."

Clinical • Combination therapy • Metastases • P2a data • Oncology • Pancreatic Cancer • Solid Tumor

ACCENT trial data presented at prestigious international conference (Amplia Therapeutics Press Release) - "A poster highlighting key data from Amplia's ongoing ACCENT trial is being presented today at the annual meeting of the American Association of Cancer Research (AACR) in Chicago, USA. The poster, presented by Amplia’s Director of Translational Science, Dr Terrie-Anne Cock, outlines the scientific rationale for the use of FAK inhibitors in pancreatic cancer treatment, describes the clinical design of the ACCENT trial, and presents a detailed analysis of data up to 7 March 2025 for the first 29 patients of the 55 enrolled in the trial."

P1/2 data • Pancreatic Ductal Adenocarcinoma

US clinical trial activities for narmafotinib now underway (Amplia Therapeutics Press Release) - "Amplia has announced that trial initiation activities for the planned pancreatic cancer trial in the US have begun. This new trial will explore the combination of the Company’s best-in-class FAK inhibitor narmafotinib with the chemotherapy FOLFIRINOX in patients with advanced pancreatic cancer."

New trial • Pancreatic Cancer

ENCOURAGING UPDATED DATA FROM PANCREATIC CANCER TRIAL (Amplia Therapeutics Press Release) - P1b/2a | N=62 | ACCENT (NCT05355298) | Sponsor: Amplia Therapeutics Limited | "Amplia Therapeutics Limited...is pleased to report updated data from the Company’s ongoing Phase 2a clinical trial....A total of 55 advanced pancreatic patients have enrolled in the study at the trial sites in Australia and Korea. The trial is fully enrolled and as of 12 March 2025, 29 patients remain on study....At this time, 13 confirmed partial responses (PRs) have been observed (defined as a >30% reduction in tumour size sustained over two months with no new lesions apparent), noting that tumour shrinkage assessments for the majority of patients enrolled since December are yet to be undertaken...Narmafotinib in combination with chemotherapy demonstrates good tolerability, with adverse event profiles similar to chemotherapy alone. Additional ACCENT trial data has been accepted for presentation at the American Association of Cancer Research Annual Meeting in April."

P2a data • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma

Pulsed priming with narmafotinib reduces fibrosis and enhances both gemcitabine/Abraxane & FOLFIRINOX response in pancreatic cancer (LCC 2025) - "Sponsored by millenium science, MCE (MedChemExpress) and CELLECTA."

Fibrosis • Hepatology • Immunology • Oncology • Pancreatic Cancer • Solid Tumor

Pulsed priming with narmafotinib reduces fibrosis and enhances both gemcitabine/Abraxane & FOLFIRINOX response in pancreatic cancer (LCC 2025) - P1, P1/2 | "The potential utility of narmafotinib is further supported by Phase I safety data (ACTRN12620000894998) showing excellent safety, tolerability, and pharmacokinetic properties following oral administration in human volunteers. Collectively, our pre-clinical results using this Phase II drug combination, strongly support the clinical assessment of narmafotinib in combination with chemotherapy in pancreatic cancer, which is currently ongoing in Phase Ib/IIa clinical trials, assessing a pulse dosing regimen of narmafotinib in combination with gemcitabine and Abraxane as first-line therapy in patients with unresectable or metastatic pancreatic cancer and warrants future assessment of narmafotinib in human PDAC patients."

Fibrosis • Hepatology • Immunology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

COMPLETION OF RECRUITMENT OF ACCENT TRIAL (Amplia Therapeutics Press Release) - "Amplia Therapeutics Limited...is pleased to announce that the ACCENT trial in advanced pancreatic cancer is now fully enrolled. The two-stage ACCENT trial explores the use of the Company’s best-in-class FAK inhibitor narmafotinib in combination with standard-of-care chemotherapy in first-line patients with advanced pancreatic cancer....As of this date the total number of patients remaining on study is 35....Full recruitment has been achieved 2 months ahead of schedule with top-line data now planned for release mid-Q3."

Enrollment closed • P2a data • Pancreatic Ductal Adenocarcinoma

ACCENT: AMP945 in Combination with Nab-paclitaxel and Gemcitabine for Treatment of Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=62 | Active, not recruiting | Sponsor: Amplia Therapeutics Limited | Recruiting ➔ Active, not recruiting | Trial completion date: May 2025 ➔ May 2026 | Trial primary completion date: May 2025 ➔ May 2026

Enrollment closed • Trial completion date • Trial primary completion date • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Next & Bio, Australia's Amplia Sign Joint Research Agreement for New Pancreatic Cancer Drug [Google translation] (Hankyung) - "Next & Bio announced on the 13th that it has signed a joint research agreement with Australian pharmaceutical company Amplia Therapeutics and will begin joint research to develop a new drug for pancreatic cancer....Under this agreement, Next&Bio will conduct joint research with AmpliA based on organoids of pancreatic cancer patients with six KRAS mutations. KRAS, a mutation of the 'RAS protein' that causes cancer, is found in 95% of pancreatic cancer. Next&Bio will collect a small amount of cancer tissue from KRAS-mutated pancreatic cancer patients to create organoids and conduct a drug evaluation of AmpliA's anticancer drug candidate, 'Narmafotinib (AMP945)'."

Licensing / partnership • Pancreatic Cancer

TUMOUR RESPONSE IN SIXTH PATIENT TRIGGERS ADDITIONAL RECRUITMENT IN PANCREATIC CANCER TRIAL (Amplia Therapeutics Press Release) - P1b/2a | N=62 | ACCENT (NCT05355298) | Sponsor: Amplia Therapeutics Limited | "Amplia Therapeutics Limited... is pleased to announce that the Company’s Phase 2a clinical trial investigating narmafotinib in the treatment of advanced pancreatic cancer (the ACCENT trial) has achieved the required response rate to support continued enrolment in the study. Six (6) patients have now recorded confirmed partial responses (PRs) out of 16 assessed at the four-month timepoint....A total of 50 patients are planned for the Phase 2a ACCENT trial. With the six (6) confirmed PRs now obtained, recruitment of the remaining 24 patients in the trial will begin at the existing open trial sites in Australia and South Korea. Recruitment of the second cohort of patients is expected to be completed by end of Q1 2025....A detailed interim analysis of the Phase 2a trial data obtained to date will be reported in the coming weeks...."

Enrollment status • P2a data • Pancreatic Cancer

FDA FAST TRACK DESIGNATION FOR NARMAFOTINIB IN ADVANCED PANCREATIC CANCER (PRNewswire) - "Amplia Therapeutics Limited...is pleased to announce that the United States Food and Drug Administration (FDA) has granted Fast Track Designation to Amplia's Focal Adhesion Kinase inhibitor, narmafotinib, for the treatment of advanced pancreatic cancer....In future, narmafotinib may be eligible for Accelerated Approval and Priority Review."

Fast track • Pancreatic Cancer

FIVE PATIENTS RECORDING A SUSTAINED REDUCTION IN TUMOUR SIZE IN ACCENT TRIAL (Amplia Therapeutics Press Release) - P1b/2a | N=62 | ACCENT (NCT05355298) | Sponsor: Amplia Therapeutics Limited | "Amplia Therapeutics Limited...is pleased to announce that a fifth patient enrolled in the Company’s Phase 2a clinical trial in pancreatic cancer...has recorded a confirmed partial response (PR), meaning a 30% or greater decrease in the overall size of tumour lesions maintained over a two-month period, and with no new tumour lesions. In addition, six (6) patients have shown stable disease (SD) at their 2 month and 4 month assessment time points. By the standard RECIST 1.1 criteria, SD is reported when tumour lesions have reduced in size by less than 30%....Only one additional confirmed response is now required to trigger the interim analysis for the first cohort in the trial....Importantly, the fifth PR has been observed from a total of 13 patients imaged at the fourmonth time point, representing an initial response rate of 38%....The Company will provide further updates on the trial as it proceeds."

P2a data • Pancreatic Cancer

Amplia receives R&D Tax Rebate (Amplia Therapeutics Press Release) - "Amplia has today announced that it has received a Research and Development Tax Incentive Refund of$3,177,718 for the 2023/2024 financial year...The refund relates to expenditure incurred in research and development associated with the Company’s FAK inhibitors, narmafotinib (AMP945) and AMP886, and are primarily related to the Company’s ongoing Phase 1b/2a clinical trial of narmafotinib in advanced pancreatic cancer patients....The Australian Government's Research and Development Tax Incentive is a program to encourage businesses to undertake research and development (R&D) activities and provides eligible companies with cash refunds for 43.5-48.5% of eligible expenditure on research and development activities."

Financing • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

ONE MORE PATIENT SHOWS SUSTAINED REDUCTION IN TUMOUR SIZE IN PANCREATIC CANCER TRIAL (Amplia Therapeutics Press Release) - P1b/2a | N=62 | ACCENT (NCT05355298) | Sponsor: Amplia Therapeutics Limited | "Amplia Therapeutics Limited...is pleased to announce that a fourth patient enrolled in the Company’s Phase 2a clinical trial investigating narmafotinib in the treatment of advanced pancreatic cancer...has recorded a confirmed partial response....In the first cohort of 26 patients, 6 or more patients with confirmed partial or complete responses are required to initiate recruitment of the second cohort of 24 patients. We have previously reported that three (3) confirmed partial responses have already been observed in the first patient cohort. This latest confirmed partial response means that only a further two (2) confirmed responses (partial or complete) are required for the trial’s interim analysis to support recruitment of the additional 24 patients in the second cohort of the trial....'We remain on track to complete the interim analysis by the end of this quarter."

P2a data • Pancreatic Cancer

SUSTAINED REDUCTION IN TUMOUR SIZE SEEN IN PATIENTS IN PANCREATIC CANCER TRIAL (Amplia Therapeutics Press Release) - P2a | N=62 | ACCENT (NCT05355298) | Sponsor: Amplia Therapeutics Limited | "Amplia Therapeutics Limited...is pleased to announce that three (3) patients enrolled in the Company’s Phase 2a clinical trial investigating narmafotinib in the treatment of advanced pancreatic cancer (the ACCENT trial) have recorded a confirmed partial response...Of the six (6) patients currently assessed at the four month time point, in addition to the three (3) confirmed partial responses, two (2) additional patients have recorded sustained stable disease...'We are well on track to reach the efficacy threshold of six confirmed partial or complete responses by the end of this quarter, which will then allow us to restart the trial to recruit the full cohort of fifty patients.'....The Company will provide further updates on the trial as recruitment proceeds."

P2a data • Trial status • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

COMPLETION OF RECRUITMENT OF FIRST 26 PATIENTS IN PHASE 2A ACCENT TRIAL (Amplia Therapeutics Press Release) - "Amplia Therapeutics Limited...is pleased to announce that it has now recruited 26 patients in the Phase 2a stage of its clinical trial investigating narmafotinib in the treatment of advanced pancreatic cancer. The ACCENT trial explores the use of narmafotinib in combination with standard-of-care chemotherapy of gemcitabine and Abraxane in first-line patients with advanced pancreatic cancer....The Phase 2a trial is being conducted using the industry-standard Simon’s Two-Stage Trial design, wherein an interim analysis of efficacy is determined at a statistically defined number of patients. In the ACCENT trial this is 26 patients. An efficacy assessment showing six or more partial or complete responses out of the 26 patients will be sufficient to continue the trial, when an additional 24 patients will be enrolled, giving a total of 50 patients."

Enrollment status • Pancreatic Cancer

Pulsed priming with narmafotinib enhances both gemcitabine/Abraxane & FOLFIRINOX response in pancreatic cancer (EACR 2024) - "Long-term assessment in patient-derived models demonstrates that narmafotinib priming prior to gemcitabine/Abraxane or FOLFIRINOX reduces PDAC progression and extends survival in both chemotherapy settings.Conclusion Our results using these Phase II-ready drug combinations strongly support the clinical assessment of narmafotinib in PDAC. Narmafotinib is currently in Phase Ib/IIa trials, assessing a pulsed dosing regimen prior to gemcitabine/Abraxane, and warrants future clinical assessment of narmafotinib in combination with FOLFIRINOX."

Fibrosis • Gastrointestinal Cancer • Hepatology • Immunology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Phase 1b/2a of narmafotinib (AMP945) in combination with gemcitabine and nab-paclitaxel in first-line patients with advanced pancreatic cancer (ACCENT trial): Interim analysis. (ASCO 2024) - P1/2 | "Based on this promising Phase 1b data, 400 mg of narmafotinib has been selected for the RP2D and Part B of the trial is now underway and recruiting patients in Australia and South Korea. The trial will enrol up to 50 patients as part of the Phase 2 expansion cohort. Clinical trial information: NCT05355298."

Clinical • Combination therapy • Metastases • P1/2 data • Fatigue • Fibrosis • Gastrointestinal Cancer • Hepatology • Immunology • Oncology • Pancreatic Cancer • Solid Tumor

Phase 1b/2a of narmafotinib (AMP945) in combination with gemcitabine and nab-paclitaxel (Abraxane) standard of care as first-line therapy in patients with advanced pancreatic cancer (ACCENT trial): interim analysis (AACR 2024) - P1/2 | "Based on this promising Phase 1b data, 400 mg of narmafotinib has been selected for RP2D and the trial will proceed through Simon's Two Stage design and enrol up to 50 patients as part of the Phase 2 expansion cohort."

Clinical • Combination therapy • Metastases • P1/2 data • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

UPDATE ON AMPLIA’S ACCENT TRIAL IN PANCREATIC CANCER (Amplia Therapeutics Press Release) - P1b/2a | N=62 | ACCENT (NCT05355298) | Sponsor: Amplia Therapeutics Limited | "Amplia Therapeutics Limited...is pleased to provide an update on our Phase 1b/2a trial (the ACCENT trial) of narmafotinib in combination with standard-of-care chemotherapy gemcitabine and Abraxane in first-line patients with advanced pancreatic cancer...Fourteen patients were dosed over three dose levels; A safe and well-tolerated dose of 400 mg narmafotinib once-a-day was identified that provided the drug levels to significantly inhibit FAK; Of these fourteen patients seven patients remained on trial for >6 months, with two patients being on trial for more than 10 months. By contrast, the median progression free survival for advanced pancreatic cancer patients treated with gemcitabine and Abraxane alone is 5.5 months...An interim analysis of efficacy will then be conducted around Q3 2024."

P1/2 data • Pancreatic Cancer

UPDATE ON AMPLIA’S ACCENT TRIAL IN PANCREATIC CANCER (Amplia Therapeutics Press Release) - "The Phase 2a trial will initially enrol 26 patients over the coming months. Recruitment into this next stage of the trial is progressing well recruiting patients through six trial sites in Australia and five trial sites in South Korea. Currently eleven patients have now been recruited. Seven patients in Australia and four patients in Korea....An efficacy assessment showing six or more partial or complete responses out of the 26 patients will be sufficient to continue the trial. An additional 24 patients will then be enrolled to give a total of 50 patients."

Trial status • Pancreatic Cancer

Focal adhesion kinase inhibitors as maintenance therapy in a homologous recombination repair proficient high-grade serous ovarian cancer murine model (SGO 2024) - "All mice received intraperitoneal cisplatin 3mg/kg and paclitaxel 5mg/kg twice weekly for a total of three weeks after confirmation of tumor growth. Conclusion In a homologous recombination repair proficient HGSOC murine model, AMP945 FAK inhibitor as maintenance therapy was superior to niraparib at controlling tumor burden. Future studies are needed to investigate the efficacy of AMP945 as maintenance therapy over longer study durations and against other therapeutics, with the hope of ultimately translating this into clinical practice to improve cancer outcomes."

Preclinical • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • BRCA • HRD • KRAS • PD-L1 • PVR

ACCENT: AMP945 in Combination With Nab-paclitaxel and Gemcitabine for Treatment of Pancreatic Cancer (clinicaltrials.gov) - P1/2 | N=62 | Recruiting | Sponsor: Amplia Therapeutics Limited | Phase classification: P1b/2a ➔ P1/2

Combination therapy • Phase classification • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor

Amplia Therapeutics moves to next phase of pancreatic cancer treatment trial (Yahoo Finance) - "Amplia Therapeutics Ltd...CEO Chris Burns joins Proactive’s Jonathan Jackson to discuss the company’s busy quarter and what investors can expect over the coming months....Korean drug regulators have approved the company’s application to conduct the ACCENT trial in that country and Korean sites are ready to recruit patients."

Trial status • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor