On September 15, 2024 Akeso reported the Phase 2 clinical results of its internally developed PD-1/VEGF bispecific antibody, ivonescimab, with or without ligufalimab (anti-CD47 antibody AK117) for the first-line treatment of PD-L1-positive (CPS≥1) recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Conference (Press release, Akeso Biopharma, SEP 15, 2024, View Source [SID1234646631]).

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At the data cut-off date of March 19, 2024, results indicate that for HNSCC with a high need for rapid tumor reduction, the ivonescimab regimen has demonstrated clinically meaningful reduction in tumor size. When combined with ligufalimab, both tumor shrinkage and survival benefits demonstrated further improvement from ivonescimab alone. Both ivonescimab alone and the ivonescimab plus ligufalimab combination have achieved preliminary efficacy data that surpassed previously disclosed PD-1 studies.

The objective response rate (ORR) for ivonescimab monotherapy group is 30%, while the ORR increases to 60% in ivonescimab plus ligufalimab group. The disease control rate (DCR) is 80% for ivonescimab monotherapy group improves to 90% with ligufalimab. As of the report time, the antitumor efficacy of the ivonescimab continues to be promising, with some patients showing an improvement from stable disease (SD) to partial response (PR). The ORR for ivonescimab monotherapy and the combination of ivonescimab plus ligufalimab was to 40% and 65%, respectively.
The median progression-free survival (mPFS) for ivonescimab monotherapy group was 5.0 months, with the 6-month PFS rate not yet reached. For the combination with ligufalimab group, the mPFS was 7.1 months, with a 6-month PFS rate of 71.8%.
The safety profile of the ivonescimab for first-line treatment of PD-L1-positive R/M HNSCC was manageable, with no treatment-related adverse events (TRAE) leading to drug discontinuation or death in both the ivonescimab monotherapy and the ivonescimab plus ligufalimab groups.
Although programmed cell death protein 1 (PD-1) inhibitors combined with chemotherapy are approved as first-line treatments for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), some patients exhibit poor responses to this approach, highlighting the need for new treatment strategies. Akeso has initiated a phase 3 clinical study comparing ivonescimab combined with ligufalimab versus pembrolizumab for the first-line treatment of PD-L1 positive R/M HNSCC. This study offers the potential to provide a new, highly effective immunotherapy option for these patients and may pave the way for the advancement of cancer immunotherapy 2.0.

On September 15, 2024 Akeso reported efficacy data for the first time for its internally developed PD-1/VEGF bispecific antibody, ivonescimab, with or without ligufalimab (anti-CD47 antibody AK117) , in combination with FOLFOXIRI as a first-line (1L) treatment for metastatic colorectal cancer (mCRC) (Press release, Akeso Biopharma, SEP 15, 2024, View Source [SID1234646630]). The principal investigator of the study, Professor Yanhong Deng from the Sixth Affiliated Hospital of Sun Yat-Sen University, delivered an oral presentation at the conference.

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Microsatellite stable (MSS) and mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) tumors have long been considered "immunological deserts," with prior attempts at immunotherapy offering minimal benefits. The current standard first-line treatment for MSS/pMMR mCRC patients remains a combination of chemotherapy with bevacizumab or cetuximab, which has shown limited therapeutic efficacy.

As of February 29, 2024, the median follow-up time for the ivonescimab plus ligufalimab combination with FOLFOXIRI group was 9.6 months, and 9.0 months for the ivonescimab plus FOLFOXIRI group. Results indicated that both regimens demonstrate high anti-tumor activity and effective disease control for first-line treatment of MSS/pMMR mCRC, with promising preliminary long-term outcomes. Notably, the combination of ivonescimab with ligufalimab showed superior anti-tumor efficacy, with preliminary data from both groups significantly surpassing existing standard treatments.

For first-line treatment of MSS/pMMR mCRC with ivonescimab, either alone or in combination with ligufalimab and FOLFOXIRI, the objective response rate (ORR) was 88.2%, and the disease control rate (DCR) was 100%. At a median follow-up of 9.6 months, the median progression-free survival (mPFS) has not yet been reached, with a 9-month PFS rate of 86.2%.

In the first-line treatment of MSS/pMMR mCRC with ivonescimab combined with FOLFOXIRI, the ORR was 81.8% and the DCR was 100%. At a median follow-up of 9 months, the median PFS has not yet been reached, with a 9-month PFS rate of 81.4%.

Both groups demonstrated acceptable safety profiles, with manageable treatment-related adverse events (TRAEs).

The study results support further evaluation of ivonescimab, either alone or in combination with ligufalimab, with chemotherapy for first-line treatment of MSS/pMMR mCRC.

On September 15, 2024 ImmVira reported the latest clinical results for its lead oncolytic virus product, MVR-T3011, via intravesical administration in patients with high-risk BCG-failure non-muscle invasive bladder cancer (NMIBC) (Press release, Immvira, SEP 15, 2024, View Source;immvira-unveils-clinical-results-of-intravesical-mvr-t3011-for-high-risk-bcg-failure-nmibc-patients-302248442.html [SID1234646629]). The results were published through poster presentation at the 2024 European Society for Medical Oncology (ESMO 2024).

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This Phase I, open-label, dose-escalation and expansion study was conducted in China to assess the safety and efficacy of MVR-T3011 administered intravesically in patients with high-risk BCG-failure NMIBC. The study enrolled a broader patient population, including those with high-grade Ta, T1, or CIS +/- Ta/T1 bladder cancer, regardless of the presence of CIS. This inclusive approach aims to target a wider range of patients, potentially accelerating future trial enrollment and expanding market opportunities. The treatment was delivered via intravesical instillation at three dose levels, with weekly induction course lasting 12 weeks, followed by bi-weekly maintenance course for up to one year.

According to poster presented (cut-off as of June 27, 2024), among 14 evaluable patients, the overall 3-month complete response (CR) rate across all dose levels was 71.4% (10/14). At the 2×109 PFU dose level (expected RP2D), the CR rate reached an impressive 87.5% (7/8). The study showed a favorable safety profile, with no dose-limiting toxicities (DLTs) reported and no maximum tolerated dose (MTD) reached. Additionally, MVR-T3011 treatment simplifies clinical procedure by eliminating the need for bladder prewash by nature, further reducing patient discomfort. The instillation process is both quick and efficient.

By September 15, 2024, the most recent data shows that 20 subjects have received MVR-T3011 treatment. At the RP2D dose level, the 3-month CR rate remained strong at 81.8% (9/11). Of the 9 patients who have reached the 6-month assessment, 8 have maintained CR, while 4 patients have reached the 9-month assessment and all remained in CR. We are continuing to gather additional data to support further analysis.

"There is a significant unmet need for innovative treatments for bladder cancer," said Dr. Grace Zhou, Chairwoman and CEO of ImmVira. "We are highly encouraged by the preliminary safety and efficacy data from this Phase I study, especially the 3-month CR rate over 80%, along with durable responses at 6- and 9-month time points. With this early success, we are committed to accelerating clinical development of intravesical MVR-T3011 treatments for BCG-failure NMIBC patients and exploring its potential across other bladder cancer indications. Our goal is to provide a novel, effective, and well-tolerated treatment solution for patients."

About MVR-T3011

MVR-T3011, ImmVira’s proprietary 3-in-1 oHSV, is a novel genetic engineered oHSV with advanced backbone design aiming to achieve the most favorable profile of attenuated HSV-1 with replication potency in tumor cells and highly restricted replication in normal cells, supporting intratumoral, intravenous and intravesical administrations. Additionally, MVR-T3011 incorporated two latest and well-validated exogenous genes, PD-1 antibody and IL-12, to further enhance immune responses in the tumor microenvironment.

On September 15, 2024 TORL BioTherapeutics, LLC ("TORL Bio" or "the Company"), a clinical stage biotechnology company discovering and developing new antibody-based immunotherapies to improve and extend the lives of patients with cancer worldwide, reported the presentation of additional results from the ongoing Phase 1 study of TORL-1-23, the Company’s Claudin 6 (CLDN6) targeted antibody-drug conjugate (ADC) in patients with advanced cancer at the 2024 European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (ESMO 2024) in Barcelona, Spain (Press release, TORL Biotherapeutics, SEP 15, 2024, View Source [SID1234646628]). This mini-oral presentation (ESMO Presentation #721MO) included updated results from the TORL123-001 (TRIO-049) trial up to the 4.0 mg/kg dose level of TORL-1-23. The data were presented by the Global Principal Investigator, Gottfried E. Konecny, M.D. of the University of California, Los Angeles (UCLA) Medical Center.

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"The latest efficacy and safety data from this Phase 1 study continue to support the potential of TORL-1-23 as a new treatment option for patients with Claudin 6 positive ovarian cancer," said Global Principal Investigator, Gottfried E. Konecny, M.D. of UCLA Medical Center.

In this ongoing Phase 1 study, 81 patients with CLND6 positive (CLDN6+), heavily pretreated ovarian, testicular, endometrial, non-small cell lung cancer (NSCLC), and other cancers were enrolled and are evaluable for safety and efficacy across 11 dose cohorts ranging from 0.2 mg/kg to 4.0 mg/kg administered intravenously every 3 weeks. Patients had an average of 4 prior therapeutic regimens.

Key study findings include the following:

At doses from 0.2 mg/kg to 2.4 mg/kg every 3 weeks, TORL-1-23 is generally well tolerated. The most common adverse events were grade 1 or 2 fatigue, peripheral neuropathy, and alopecia. The most frequent grade 3+ adverse event was neutropenia. Febrile neutropenia, interstitial lung disease, and ocular toxicities were not observed.
Prophylactic pegfilgrastim was implemented at doses 3.0 mg/kg or higher and was effective at mitigating neutropenia. The maximum tolerated dose (MTD) has yet to be identified.
Encouraging antitumor activity was observed in this heavily pretreated population during dose finding across all enrolled cancer histologies and dose levels.
At doses of 2.4 mg/kg and 3.0 mg/kg every 3 weeks, there were deep and durable confirmed responses in 9/20 (45%) patients with CLDN6+ platinum-resistant/refractory ovarian cancer (PROC). Median duration of response exceeded 6 months at both dose levels.
"The objective of molecularly targeted therapeutics in cancer is to significantly enhance efficacy while simultaneously maintaining or improving safety over established treatments. The emerging Phase 1 profile of TORL-1-23 suggests that this ADC may achieve that goal for patients with platinum-resistant ovarian cancer, a serious unmet medical need," said Scientific Co-founder Dennis Slamon, MD, PhD, Professor of Medicine, and Chief of the Division of Hematology/Oncology at UCLA’s David Geffen School of Medicine.

Phase 1 evaluation of TORL-1-23 in NSCLC and other CLDN6+ cancers is ongoing. A multi-dose Phase 2 study that is designed to support accelerated registration in CLDN6+ PROC is being initiated.

Presentation Details

Title: Phase 1, Two-Part, Multicenter First-In-Human (FIH) Study of TORL-1-23, A Novel Claudin 6 (CLDN6) Targeting Antibody Drug Conjugate (ADC) In Patient with Advanced Solid Tumors
Lead Author: Gottfried Konecny, M.D., UCLA Medical Center
Presentation Number: 721MO
Presentation Session: Mini Oral Session 2: Gynaecological cancers
Presentation Session Date and Time: September 15, 2024, at 15:50 CEST

About Claudin 6

Claudin 6 (CLDN6) is overexpressed in multiple cancers with limited to no detectable expression observed in normal tissues, thus an ideal target for antibody-drug conjugate development. CLDN6 is a tumor-specific transmembrane protein of tight junctions important for cell-to-cell connectivity. Overexpression of CLDN6 is implicated in the initiation, progression, and metastasis of certain cancers, including ovarian, non-small cell lung, endometrial, testicular and others. High expression correlates with shortened survival outcomes for patients with ovarian cancer.

About TORL-1-23

TORL-1-23 is a first and potentially best-in-class clinical-stage antibody-drug conjugate (ADC) for the treatment of Claudin 6 positive (CLDN6+) solid tumors. Select centers are enrolling patients in the Part 2 expansion of Phase 1 study TORL123-001 (TRIO-049), assessing the safety, pharmacokinetics, biomarkers, and antitumor activity of TORL-1-23. Further details including current study sites can be found at View Source

On September 15, 2024 AstraZeneca reported positive results from the NIAGARA Phase III trial showed AstraZeneca’s Imfinzi (durvalumab) in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of event-free survival (EFS) and the key secondary endpoint of overall survival (OS) versus neoadjuvant chemotherapy for patients with muscle-invasive bladder cancer (MIBC) (Press release, AstraZeneca, SEP 15, 2024, View Source [SID1234646625]). Patients were treated with Imfinzi in combination with neoadjuvant chemotherapy before radical cystectomy (surgery to remove the bladder) followed by Imfinzi as adjuvant monotherapy.

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These results will be presented today during a Presidential Symposium at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in Barcelona, Spain (abstract #LBA5) and simultaneously published in The New England Journal of Medicine.

In a planned interim analysis, patients treated with the Imfinzi perioperative regimen showed a 32% reduction in the risk of disease progression, recurrence, not undergoing surgery, or death versus the comparator arm (based on EFS hazard ratio [HR] of 0.68; 95% confidence interval [CI] 0.56-0.82; p<0.0001). Estimated median EFS was not yet reached for the Imfinzi arm versus 46.1 months for the comparator arm. An estimated 67.8% of patients treated with the Imfinzi regimen were event free at two years compared to 59.8% in the comparator arm.

Results from the key secondary endpoint of OS showed the Imfinzi perioperative regimen reduced the risk of death by 25% versus neoadjuvant chemotherapy with radical cystectomy (based on OS HR of 0.75; 95% CI 0.59-0.93; p=0.0106). Median survival was not yet reached for either arm. An estimated 82.2% of patients treated with the Imfinzi regimen were alive at two years compared to 75.2% in the comparator arm.

Professor Thomas Powles, MD, Director of Barts Cancer Centre (QMUL), London, UK, and principal investigator in the NIAGARA trial, said: "Neoadjuvant chemotherapy with bladder removal has been the mainstay of treatment for patients with muscle-invasive bladder cancer for nearly twenty years; however, half of patients still go on to suffer a devastating recurrence. Adding durvalumab before and after surgery significantly reduced the chance of recurrence and extended survival, a significant advance with the potential to transform the standard of care for these patients who desperately need better outcomes."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "The NIAGARA data showed compelling improvements in both event-free survival and overall survival, with more than 80 per cent of patients treated with the Imfinzi perioperative regimen alive at two years. This is the first immunotherapy regimen to significantly extend overall survival in muscle-invasive bladder cancer, and it further validates our strategy to move cancer treatment as early as possible to maximise benefit for patients."