On September 16, 2024 Instil Bio, Inc. (Nasdaq: TIL, "Instil") and ImmuneOnco Biopharmaceuticals (Shanghai) Inc. (HKEX:1541, "ImmuneOnco") reported the global registrational strategy for the PD-L1xVEGF bispecific antibody SYN-2510/IMM2510 in combination with chemotherapy in front-line non-small cell lung cancer (NSCLC) and in front-line triple-negative breast cancer (TNBC) (Press release, Instil Bio, SEP 16, 2024, View Source [SID1234646655]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In China, ImmuneOnco is accelerating the development of IMM2510/SYN-2510 in front-line NSCLC by targeting initiation in late 2024 of a Phase 1b/2 front-line chemo combination study. This study is expected to enroll patients with driver gene mutation-negative non-squamous and squamous NSCLC. ImmuneOnco is also accelerating development of IMM2510/SYN-2510 in front-line TNBC with initial Phase 1b/2 chemotherapy combination studies targeted to begin in early 2025.

In the United States, Instil is prioritizing development of SYN-2510/IMM2510 in NSCLC and TNBC. US IND submission is targeted for late 2024, starting with a Phase 2 trial of SYN-2510/IMM2510 monotherapy in second-line non-squamous and squamous NSCLC.

With potential positive proof-of-concept data, ImmuneOnco and Instil may initiate joint global randomized Phase 3 chemotherapy combination trials in first-line non-squamous and squamous NSCLC and/or first-line TNBC.

"There are significant unmet medical needs in NSCLC and TNBC cancer patients which may be addressed by IMM2510," said Dr. Wenzhi Tian, PhD, CEO and CSO of ImmuneOnco. "This practical and accelerated registrational strategy, which is aligned with Instil, paves a clear pathway to a potential regulatory approval for us in China and for Instil Bio globally."

"SYN-2510 may have the opportunity to meaningfully improve on the current standard of care in NSCLC and TNBC," said Bronson Crouch, CEO of Instil. "Our expectation for the initial US study of SYN-2510 is that it would lay a foundation for the efficient enrollment of potential global Phase 3 studies."

About SYN-2510/IMM2510

SYN-2510/IMM2510 is a PD-L1xVEGF bispecific antibody in development for the treatment of multiple solid tumor cancers. SYN-2510/IMM2510 is differentiated from other PD-(L)1xVEGF bispecific antibodies by its VEGF trap, which binds multiple VEGF receptor ligands beyond VEGF-A, a bispecific structure which leverages PD-L1 as an anchor in the tumor microenvironment (TME), and enhanced antibody-dependent cellular cytotoxicity (ADCC) to direct killing of PD-L1-positive tumor cells.

On September 16, 2024 Aethlon Medical, Inc. (Nasdaq: AEMD), a medical therapeutic company focused on developing products to treat cancer and life-threatening infectious diseases, reported that the Cancer Clinical Trial Unit at Royal Adelaide Hospital was activated on September 10, 2024 to begin screening and enrolling patients in its safety, feasibility and dose-finding clinical trial of the Hemopurifier in patients with solid tumors who have stable or progressive disease during anti-PD-1 monotherapy treatment, such as Keytruda (pembrolizumab) or Opdivo (nivolumab) (AEMD-2022-06 Hemopurifier Study) (Press release, Aethlon Medical, SEP 16, 2024, View Source [SID1234646672]). The trial will be conducted by Prof. Michael Brown and his staff at the Cancer Clinical Trials Unit, CALHN, Royal Adelaide Hospital in Australia.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The activation follows the previously announced approval by the Human Research Ethics Committee at Central Adelaide Local Health Network on June 13, 2024, and the Research Governance office at Royal Adelaide Hospital, on September, 3 2024, as well as the notification of the Therapeutic Good Administration (TGA) and completion of a Site Initiation Visit on September 9, 2024.

"The activation of the investigative site at the Royal Adelaide Hospital marks a significant milestone for Aethlon, allowing the site to screen and enroll patients in this important clinical trial," stated Steven LaRosa, MD, Chief Medical Officer of Aethlon Medical. "We look forward to working closely with Prof. Brown and his staff, and with our Contract Research Organizations (CROs), NAMSA and ReSQ Clinical Research, to begin enrollment and data collection. Going forward, we plan to activate a second site in Australia and also expect to receive an Ethics Committee approval for a clinical site in India."

Currently, only approximately 30% of patients who receive pembrolizumab or nivolumab will have lasting clinical responses to these agents. Extracellular vesicles (EVs) produced by tumors have been implicated in the spread of cancers as well as the resistance to anti-PD-1 therapies. The Aethlon Hemopurifier has been designed to bind and remove these EVs from the bloodstream, which may improve therapeutic response rates to anti-PD-1 antibodies. In preclinical studies, the Hemopurifier has been shown to reduce the number of exosomes from the plasma of cancer patient samples.

The primary endpoint of the approximately 18-patient, safety, feasibility and dose-finding trial is the incidence of adverse events and clinically significant changes in safety lab tests of Hemopurifier treated patients with solid tumors with stable or progressive disease at different treatment intervals, after a two-month run in period of PD-1 antibody, Keytruda or Opdivo monotherapy. Patients who do not respond to the therapy will be eligible to enter the Hemopurifier period of the study where sequential cohorts will receive 1, 2 or 3 Hemopurifier treatments during a one-week period. In addition to monitoring safety, the study is designed to examine the number of Hemopurifier treatments needed to decrease the concentration of EVs and whether these changes in EV concentrations improve the body’s own natural ability to attack tumor cells. These exploratory central laboratory analyses are expected to inform the design of a subsequent efficacy and safety, Premarket Approval (PMA), study required by regulatory agencies.

On September 16, 2024 Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and genetic testing, reported the simultaneous publication of three peer-reviewed papers, crossing a milestone of more than 85 peer-reviewed publications on Signatera (Press release, Natera, SEP 16, 2024, View Source [SID1234646688]).
This includes:

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Groundbreaking colorectal cancer (CRC) data from the GALAXY arm of the ongoing CIRCULATE-Japan trial, published today in Nature Medicine, and also available in Poster Presentation #553P at the 2024 Congress of the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) in Barcelona, Spain.
Additional CRC data from GALAXY, published today in Annals of Oncology, and also available in Poster Presentation #558P at ESMO (Free ESMO Whitepaper).
A new paper from the BELLINI trial, published today in Nature Medicine, investigating the feasibility and potential efficacy of immune checkpoint inhibitors (ICI) without concurrent chemotherapy in triple negative breast cancer (TNBC).
CRC Data from GALAXY (Nature Medicine & ESMO (Free ESMO Whitepaper) Poster)

In this study, 2,240 patients with stage II– IV CRC were monitored using Signatera after curative-intent surgery with a median follow-up of 23 months. This data provides the first evidence of Signatera-based molecular residual disease (MRD) detection to predict overall survival (OS) and highlights Signatera’s ability to predict adjuvant chemotherapy (ACT) benefit. Full details on the data are available here, as announced on Sept. 14, 2024.

CRC Data from GALAXY (Annals of Oncology & ESMO (Free ESMO Whitepaper) Poster)

This study retrospectively analyzed 190 patients enrolled in GALAXY who underwent surgical resection for colorectal liver metastases and underscores Signatera’s ability to risk-stratify CRC patients. Of the patients who were Signatera-positive within 2-10 weeks after surgical resection, 24-month disease free survival (DFS) was superior for those who received ACT compared to patients on observation, whereas no statistically significant benefit of ACT was observed among Signatera-negative patients.

Breast Cancer Data from Bellini Trial (Nature Medicine)

This study reports initial results from the BELLINI trial, a phase 2 study that enrolled 43 patients with stage I-III triple-negative breast cancer (TNBC). Patients in the study underwent short-term (2-3 cycles) of nivolumab, alone or in combination with ipilimumab, prior to standard-of-care neoadjuvant chemotherapy or surgery. Circulating tumor DNA (ctDNA) analysis with Signatera was performed before treatment and after 4 or 6 weeks of treatment. All clinical responders including patients who achieved pathologic complete response demonstrated at least a 50% decrease in ctDNA levels, or were ctDNA-negative at baseline.

"We are extremely proud to announce the publication of these datasets in top-tier medical journals, underscoring the breadth of clinical evidence we continue to build on the utility of Signatera," said Alexey Aleshin, MD, MBA, general manager of oncology and chief medical officer of Natera. "The first overall survival readout in colorectal cancer from GALAXY marks a landmark moment that may fundamentally change how resectable colorectal cancer is managed for the hundreds of thousands of patients at risk of recurrence each year. We are especially grateful to the patients who participated in these trials, as well as our collaborators and study investigators for their dedication to improving outcomes for patients."

About Signatera

Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard of care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer, ovarian cancer and muscle invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 85 peer-reviewed papers.

On September 16, 2024 Ipsen (Euronext: IPN; ADR: IPSEY) reported final data from the CABINET Phase III trial investigating Cabometyx (cabozantinib) versus placebo in people living with advanced pancreatic neuroendocrine tumors (pNETs) or advanced extra-pancreatic neuroendocrine tumors (epNETs) whose disease had progressed after prior systemic therapy (Press release, Ipsen, SEP 16, 2024, View Source [SID1234646657]). These data demonstrated a statistically significant reduction in the risk of disease progression or death for Cabometyx versus placebo of 77% (hazard ratio (HR) 0.23) and 62% (HR 0.38) for people living with advanced pNETs and epNETs, respectively.1,2 Presentation of these data is taking place today at the 2024 European Society for Medical Oncology Congress (ESMO 2024) during the Proffered Paper Session: NETs and Endocrine Tumors at 2:45 p.m. CEST, and is published in the New England Journal of Medicine (NEJM).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"People living with neuroendocrine tumors face many challenges, from securing a timely diagnosis to optimal treatment options which address the needs of the increasing number of people affected by this cancer worldwide," said Teodora Kolarova, Executive Director, International Neuroendocrine Cancer Alliance. "These latest data reaffirm the possibilities of continuing scientific advancements in neuroendocrine tumors, offering the potential for new therapies which could significantly impact people’s everyday lives as they navigate this complex and life altering diagnosis."

Final results demonstrated progression-free survival (PFS) benefits in favor of Cabometyx versus placebo by blinded independent central review (BICR).1,2 In the pNET cohort, at a median follow-up of 13.8 months, median PFS was 13.8 months for Cabometyx versus 4.4 months for placebo (HR 0.23 [95% confidence interval (CI) 0.12-0.42] p<0.0001).1,2 In the epNET cohort, at a median follow-up of 10.2 months, median PFS was 8.4 months for Cabometyx versus 3.9 months for placebo (HR 0.38 [95% CI 0.25-0.59] p<0.0001).1,2 The safety profile of Cabometyx observed in each cohort was consistent with its known safety profile; no new safety signals were identified.1,2

"These latest data reinforce the potential of Cabometyx to deliver significant efficacy benefits at an advanced stage of disease," said Christelle Huguet, EVP and Head of Research and Development at Ipsen. "Through our submission to the EMA, it is our ambition to evolve the treatment paradigm for people living with neuroendocrine tumors, harnessing our longstanding heritage in this area to deliver an effective new therapy where options are notably limited."

The number of people newly diagnosed with NETs is believed to be rising due to increasing awareness and better methods of diagnosis, with approximately 35 in every 100,000 people currently living with NETs globally.5,6 However, despite increasing awareness, the non-specific nature of NET symptoms often leads patients to be seen by multiple specialists and to undergo various forms of testing before an accurate diagnosis is achieved.5 As a result, almost a third of people take at least five years to be diagnosed with NETs, contributing to poorer patient outcomes.5 Most forms of NETs are indolent in nature and can develop in any part of the body,7 requiring multiple lines of therapy as people progress.3,4 Treatment options upon progression are often limited dependent on primary site of disease, resulting in challenges in identifying optimal care pathways specific to patients’ circumstances.

On September 16, 2024 Trishula Therapeutics, Inc., a clinical stage, privately held biotechnology company, reported final results from a Phase 1 trial of TTX-030, a potential first-in-class, anti-CD39 antibody, in patients with first-line metastatic pancreatic cancer (Press release, Trishula Therapeutics, SEP 16, 2024, View Source [SID1234646673]). Results were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 in Barcelona, Spain.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The Phase 1 results demonstrated a strong median overall survival in patients with metastatic pancreatic cancer following treatment with TTX-030 combinations as well as marked benefit in those with high levels of tumor HLA-DQ biomarker expression," said Anil Singhal, Chief Executive Officer of Trishula Therapeutics. "These findings have led to our currently enrolling global, randomized Phase 2 ELTIVATE study with results expected in 2026."

The Phase 1 trial evaluated TTX-030 in combination with gemcitabine/nab-paclitaxel, with or without budigalimab (an investigational anti-PD-1 antibody), as first-line treatment for pancreatic adenocarcinoma. In the efficacy-evaluable population (n=57) consisting of 92% first-line metastatic and 8% locally advanced nonresecetable patients, the objective response rate (ORR) was 30%, with 3 complete responses; the median progression free survival (mPFS) was 7.5 months (95%CI 5.2, 9.4); and median overall survival was 19.1 months (9.8, NR). Analysis of pre-treatment tumor biopsies identified a subset of patients with a high expression of an immune-associated biomarker, HLA-DQ (HLA-DQhigh) and favorable clinical outcomes with TTX-030 combinations. Of the 28 HLA-DQhigh patients, the ORR was 46%, mPFS was 9.6 months (95% CI 3.9, 11.8), and mOS of 21.9 months (9.8, NR).

Both treatment combinations were well-tolerated, with only five patients (8%) discontinuing treatment due to adverse events (AEs). The most frequent AEs were those expected from the standard of care chemotherapy backbone without an increase in frequency or severity.

"Prior evaluation of immune checkpoint treatment has demonstrated limited benefit in this patient population and new approaches are needed. These results are very encouraging, especially in the biomarker high patients and warrant further investigation of TTX-030 for patients with advanced pancreatic cancer," said Zev Wainberg, MD, Professor of Medicine, UCLA.

TTX-030 is currently being evaluated as first-line treatment for metastatic pancreatic adenocarcinoma in the global Phase 2 ELTIVATE trial (NCT06119217) that is randomizing approximately 180 patients into three study arms: TTX-030 and chemotherapy (gemcitabine and nab-paclitaxel); TTX-030 plus budigalimab and chemotherapy; or chemotherapy alone. The primary endpoint of the trial is progression-free survival (PFS) in a biomarker-enriched (HLA-DQhigh) population. Secondary endpoints include PFS in the overall population, safety, objective response rate, duration of response and overall survival. Further information on the study can be found at (clinicaltrials.gov link).

About TTX-030

TTX-030 is a potential first-in-class, anti-CD39 antibody designed to inhibit the activity of CD39, an enzyme that converts adenosine triphosphate (ATP) to adenosine monophosphate (AMP), the initial step in the generation of adenosine in the tumor microenvironment. TTX-030 prevents the formation of immune-suppressive extracellular adenosine and maintains high levels of immune-activating extracellular ATP, stimulating dendritic and myeloid-derived cells promoting both innate and adaptive anti-tumor immunity.

Trishula is continuing to develop TTX-030 in collaboration with AbbVie Inc.