On July 12, 2024 Senhwa Biosciences’ reported that its new drug Pidnarulex (CX-5461) has demonstrated efficacy in treating various solid tumors with BRCA2 or PALB2 gene defects (Press release, Senhwa Biosciences, JUL 12, 2024, View Source;data-abstract-of-pidnarulex-accepted-for-presentation-at-2024-esmo-congress-302195586.html [SID1234644809]). The abstract of this clinical trial has been selected for presentation at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) congress. This achievement is a significant milestone for Senhwa Biosciences and the Canadian clinical team, as it includes terminal cancer patients who although have undergone various prior treatments are found in stable condition, continuously receiving Pidnarulex (CX-5461) treatment in this trial. This highlights that Pidnarulex (CX-5461) aligns with the trend of developing new drugs for precision medicine.

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The clinical trial is an open-label, multinational, multicenter study, divided into a Main Study Cohort and an Exploratory Cohort. The Main Study Cohort includes patients with various tumors (pancreatic cancer, breast cancer, ovarian cancer, and prostate cancer) with BRCA2 and/or PALB2 gene defects. The Exploratory Cohort includes ovarian cancer patients with BRCA1 gene defects and/or other homologous recombination deficiency (HRD) genes. The primary objective of the trial is to determine the optimal dose for patients with specific gene defects while the secondary objectives are set to assess the safety and tolerability of Pidnarulex (CX-5461), and to evaluate late-onset toxicity, antitumor activity as well as improvement in patients’ quality of life. Patients enrolled in this clinical trial have undergone 2 to 10 different treatment regimens; some of them are even resistant to platinum-based chemotherapy and PARP inhibitors, leaving no other treatment options available. Encouragingly, these terminal patients have shown clinical benefits provided by the Pidnarulex (CX-5461) treatment.

The 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress will be held from September 13 to 17, 2024, in Barcelona, Spain, welcoming both in-person and online participations. This congress will showcase the latest cutting-edge cancer translational data and provide a platform for oncology professionals and scientists to network and share research and innovations. The ESMO (Free ESMO Whitepaper) Congress is a cornerstone event in oncology, recognized globally for its significant contributions to cancer treatment and research. It is one of the top three cancer medical conferences worldwide, alongside ASCO (Free ASCO Whitepaper) and AACR (Free AACR Whitepaper). The abstract for the clinical trial of Pidnarulex (CX-5461) treating various solid tumors with BRCA1, BRCA2, and/or PALB2 gene defects (1b) was written and submitted by the Canadian clinical partner, Princess Margaret Cancer Centre. The abstract title is expected to be available online by the end of July, with the full abstract and related data to be published on September 9.

Senhwa Biosciences’ new drug, Pidnarulex (CX-5461), is currently being applied in breast cancer, ovarian cancer, pancreatic cancer, hematologic malignancies, and prostate cancer. As a new drug candidate for solid tumors in collaboration with National Institutes of Health (NIH), the first stage of clinical trials will begin in 2024. With the remarkable efforts of NIH’s professionals and medical network, Senhwa Biosciences expects the clinical outcomes of Pidnarulex (CX-5461) treating multiple cancers will make significant strides in the fight against various types of cancer.

On July 12, 2024 Mabwell (688062.SH), an innovative biopharmaceutical company with entire industry chain, reported that its self-developed novel Nectin-4-targeting ADC (R&D Code: 9MW2821) has been granted Fast Track Designation (FTD) by the U.S. Food and Drug Administration (FDA) for the treatment of locally advanced or metastatic Nectin-4 positive triple negative breast cancer (TNBC) (Press release, Mabwell Biotech, JUL 12, 2024, View Source [SID1234644808]).

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The FDA’s FTD is intended to expedite the development and review of pharmaceuticals used to treat critical conditions, therefore speeding up the process of bringing these drugs to market. Therapeutics with Fast Track Designation are likely to obtain priority evaluation and speedy approval if they meet the appropriate criteria.

9MW2821 has received multiple regulatory designations from the FDA within just 6 months. Prior to this, 9MW2821 has been granted FTD for the treatment of advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) and recurrent or metastatic cervical cancer (CC) progressed on or following prior treatment with a platinum-based chemotherapy regimen, and also granted Orphan Drug Designation (ODD) for the treatment of esophageal cancer (EC), highlighting its potential and innovation in treating multiple tumors. These designations not only accelerate the development process of 9MW2821 but also lay the groundwork for its potential future priority review.

About 9MW2821

9MW2821 is the first site-specific conjugated novel Nectin-4-targeting ADC developed by Mabwell using ADC platform and automated high-throughput hybridoma antibody molecular discovery platform, and is the first drug candidate to enter clinical study among the Nectin-4-targeting ADCs developed by Chinese companies, and the first therapeutic drug candidate targeting Nectin-4 in the world to reveal clinical efficacy data of CC, EC and breast cancer. 9MW2821 has been granted FTD by FDA for the treatment of advanced, recurrent, or metastatic ESCC in Feb. 2024, and also respectively granted ODD and FTD for the treatment of esophageal cancer and recurrent or metastatic CC progressed on or following prior treatment with a platinum-based chemotherapy regimen in May 2024. Then, it has been granted FTD for the treatment of locally advanced or metastatic Nectin-4 positive TNBC in July, 2024.

9MW2821 achieves site-specific modification of antibody through proprietary conjugate technology linkers and optimized ADC conjugation process. After injection, 9MW2821 can specifically bind to Nectin-4 on the cell membrane surface, be internalized and release cytotoxic drug, and induce the apoptosis of tumor cells.

On July 12, 2024 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported positive results from Cohort B of the TACTI-003 (KEYNOTE-PNC-34) Phase IIb trial evaluating eftilagimod alfa (efti) in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab) as first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma patients (1L HNSCC) with negative PD-L1 expression (Press release, Immutep, JUL 12, 2024, View Source [SID1234644807]). The updated efficacy and safety data was presented by Dr. Robert Metcalf during an oral presentation at the ESMO (Free ESMO Whitepaper) Virtual Plenary session at 18:30-19:30 CEST on 11 July 2024.

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Results
The investigational immuno-oncology (IO) combination utilising efti and KEYTRUDA achieved an objective response rate (ORR) of 35.5% (11 of 31 evaluable patients) and a disease control rate (DCR) of 58.1%, according to RECIST 1.1, in 1L HNSCC patients whose tumours do not express PD-L1 (Combined Positive Score [CPS] <1). These results are among the highest recorded for a chemotherapy-free approach in negative PD-L1 patients and compare favourably to a historical control of 5.4% ORR and 32.4% DCR from anti-PD-1 monotherapy.1

Additionally, the IO combination attained a high complete response rate of 9.7% (3 of 31 patients), which compares favourably to a historical control of 0% from anti-PD-1 monotherapy in 1L HNSCC patients with a CPS <1.2 Notably, one patient with early progressive disease according to RECIST 1.1 has evolved into a confirmed partial responder who remains on therapy after 14 months, resulting in a 38.7% ORR for the IO-combination, according to iRECIST.

Robert Metcalf, MD, PhD, The Christie NHS Foundation Trust, Manchester, U.K., stated, "The high response rate from this novel immunotherapy combination is well above other treatment approaches without chemotherapy. It matches historical response rates from chemotherapy-based treatments but without the associated toxicities. This is really significant for patients with head and neck squamous cell carcinomas who have a CPS less than one and for whom chemotherapy is the current first line treatment. Achieving complete responses in this group bodes well for this immunotherapy combination’s future potential, especially given the positive trend in response durability. The clinically meaningful response rate and high unmet medical need warrant further investigation of eftilagimod plus pembrolizumab in this patient population."

Durability of Responses and Favourable Safety
Durability of responses is tracking well as has been seen in other clinical trials when efti is combined with KEYTRUDA. Over 50% of patients in Cohort B received treatment for at least six months with three additional patients nearing this threshold at the time of data cut off (11 March 2024). The combination also continues to have a favourable safety profile with no new safety signals observed.

This new data adds to the body of evidence that efti’s novel activation of antigen-presenting cells provides a strong boost to the immune system, enhancing the potential of immune checkpoint inhibitors such as KEYTRUDA. Importantly, as the only MHC Class II agonist in clinical development today, efti is generating a broad anti-cancer immune response in a unique and safe manner across all levels of PD-L1 expression, especially in patients with negative expression (CPS <1).

Next Steps
Based on the encouraging efficacy and high unmet medical need, Immutep will discuss the path forward with regulatory agencies. Efti has received FDA Fast Track designation in 1L HNSCC regardless of PD-L1 expression. The prevalence for CPS <1, CPS 1-19, and CPS >20 PD-L1 expression levels are approximately 20%, 30%, and 50% of the HNSCC patient population, respectively.3

Webcast Details
Immutep will host a webcast to discuss the clinical data. A replay of the webcast will be available under the Events section of Immutep’s website after the event.

Date/Time: Friday, July 12, at 9am AEST (7pm ET July 11)
Register: Link to register for webcast
Questions: Investors are invited to submit questions in advance via [email protected]

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About the TACTI-003 Trial
The TACTI-003 (KEYNOTE-PNC-34) trial is an ongoing Phase IIb study evaluating eftilagimod alfa (efti), Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist, in combination with MSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab) as first line treatment of recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). The randomized Cohort A portion of the study is evaluating efti in combination with pembrolizumab as compared to pembrolizumab monotherapy in patients with PD-L1 positive (Combined Positive Score [CPS] ≥1) tumours, whereas Cohort B is evaluating efti in combination with pembrolizumab in patients with PD-L1 negative tumours.

The primary endpoint of the study is Overall Response Rate of evaluable patients according to RECIST 1.1. Secondary endpoints include Overall Survival, Overall Response Rate according to iRECIST, Progression Free Survival, and Duration of Response. For more information about the Phase IIb trial, visit clinicaltrials.gov (NCT04811027).

About Eftilagimod Alfa (Efti)
Efti is Immutep’s proprietary soluble LAG-3 protein and MHC Class II agonist that stimulates both innate and adaptive immunity for the treatment of cancer. As a first-in-class antigen presenting cell (APC) activator, efti binds to MHC (major histocompatibility complex) Class II molecules on APC leading to activation and proliferation of CD8+ cytotoxic T cells, CD4+ helper T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like IFN-ƴ and CXCL10 that further boost the immune system’s ability to fight cancer.

Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track designation in first line HNSCC and in first line NSCLC from the United States Food and Drug Administration (FDA).

On July 12, 2024 Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, reported that the first patient has been dosed in a Phase 1/2 trial in China, conducted by GenFleet Therapeutics, evaluating GFH375/VS-7375, a KRAS G12D (ON/OFF) inhibitor (Press release, Verastem, JUL 12, 2024, View Source [SID1234644806]).

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GFH375/VS-7375, was selected as Verastem’s lead discovery program from its collaboration with GenFleet established in 2023. GFH375/VS-7375 is an oral, potent and selective KRAS G12D dual inhibitor of ON (GTP) and OFF (GDP) states. Preclinical data presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April 2024 demonstrated oral bioavailability across preclinical species, strong anti-tumor activity as a single agent and potency against intracranial tumor models suggesting the potential to treat brain metastases.

"In a short amount of time, we identified GFH375/VS-7375, a novel KRAS G12D (ON/OFF) inhibitor, as our lead discovery program last year and now the first patient has been dosed in the Phase 1/2 study by GenFleet in China," said Dan Paterson, president and chief executive officer of Verastem Oncology. "We look forward to leveraging the initial clinical dose escalation data to accelerate our development path in the U.S., as there are currently no FDA-approved KRAS G12D-targeted treatments despite the high prevalence of this KRAS mutation in various cancers, including pancreatic, colorectal, lung and uterine."

The Phase 1 study is being conducted in approximately 20 hospitals currently in China and will evaluate the safety and efficacy of GFH375/VS-7375 in patients with advanced KRAS G12D mutant solid tumors. The Phase 1 study will determine the recommended Phase 2 dose (RP2D) and then further evaluate in Phase 2 the efficacy and safety of GFH375/VS-7375 in patients with advanced solid tumors, such as pancreatic ductal adenocarcinoma, colorectal cancer and non-small cell lung cancer.

About GFH375/VS-7375

GFH375/VS-7375 is a potential best-in-class, potent and selective oral KRAS G12D (ON/OFF) inhibitor, identified as the lead discovery program from the Verastem Oncology discovery and development collaboration with GenFleet Therapeutics. GenFleet’s IND for GFH375/VS-7375 was approved in China in June 2024 and the Phase 1/2 trial in KRAS G12D-mutant solid tumors was subsequently initiated and the first patient has been dosed in July 2024. The collaboration includes three discovery programs, the first being the KRAS G12D inhibitor, and provides Verastem Oncology with exclusive options to license three compounds selected for collaboration after successful completion of pre-determined milestones in Phase 1 trials. The licenses would give Verastem Oncology development and commercialization rights outside of the GenFleet territories of mainland China, Hong Kong, Macau, and Taiwan.

On July 12, 2024 EORTC reported that the primary endpoint has been reached in the EORTC-1333-GUCG/PEACE III Trial (Press release, EORTC, JUL 12, 2024, View Source [SID1234644802]).

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The phase III EORTC-1333-GUCG/PEACE III trial is a randomised multicentre phase III trial comparing enzalutamide vs. a combination of radium-223 dichloride and enzalutamide in asymptomatic or mildly symptomatic castration resistant prostate cancer patients metastatic to bone.

The full results will be presented at an upcoming medical meeting.

We extend our gratitude to the patients, investigators, and research teams who participated in the EORTC-1333-GUCG/PEACE III Trial and made this achievement possible.

This trial is supported by an investigator driven clinical trial agreement from Bayer HealthCare Pharmaceuticals Inc. and Astellas Pharma Europe. This trial is a collaboration between EORTC, UNICANCER, Clinical Trial Ireland (CTI), Canadian Urological Oncology Group (CUOG) and Latin American Cooperative Oncology Group (LACOG).

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