On June 4, 2024 Repare Therapeutics Inc. ("Repare" or the "Company") (Nasdaq: RPTX), a leading clinical-stage precision oncology company, reported the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to lunresertib in combination with camonsertib for the treatment of adult patients with CCNE1 amplified, or FBXW7 or PPP2R1A-mutated platinum-resistant ovarian cancer (Press release, Repare Therapeutics, JUN 4, 2024, View Source [SID1234644106]).

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Lunresertib in combination with camonsertib is currently being evaluated in Repare’s MYTHIC Module 2 Phase 1 dose expansion clinical trial at the recommended Phase 2 dose in patients with ovarian and endometrial cancers harboring CCNE1 amplification or FBXW7 or PPP2R1A mutations. In addition to the Fast Track designation announced today, the FDA previously granted Fast Track designation to lunresertib in combination with camonsertib for the treatment of adult patients with CCNE1 amplified, or FBXW7 or PPP2R1A mutated endometrial cancer in the third quarter of 2023. Repare expects to present data from the MYTHIC Module 2 dose expansion cohorts in approximately 20-30 patients each with ovarian and endometrial cancer in the fourth quarter of 2024.

"The FDA’s decision to grant Fast Track designation supports our goal of quickly and efficiently developing the lunresertib-camonsertib combination for patients with genomically-defined platinum-resistant ovarian cancer," said Maria Koehler, MD, PhD, Executive Vice President and Chief Medical Officer of Repare. "Ovarian cancer patients need therapies that provide long-term benefit beyond that observed with standard of care. Our precision medicine approach targets treatment to patients who could most benefit from a well-tolerated alternative to chemotherapy."

The FDA’s Fast Track process is designed to facilitate the development and expedite the review of therapies intended to treat serious conditions and address unmet medical needs to potentially bring important new medicines to patients earlier. Companies whose programs are granted FTD are eligible for more frequent interactions with the FDA during clinical development and potentially accelerated approval and/or priority review, if relevant criteria are met. For more information on Fast Track Designation, please visit the FDA’s website at View Source

About Repare Therapeutics’ SNIPRx Platform

Repare’s SNIPRx platform is a genome-wide CRISPR-based screening approach that utilizes proprietary isogenic cell lines to identify novel and known synthetic lethal gene pairs and the corresponding patients who are most likely to benefit from the Company’s therapies based on the genetic profile of their tumors. Repare’s platform enables the development of precision therapeutics in patients whose tumors contain one or more genomic alterations identified by SNIPRx screening, in order to selectively target those tumors in patients most likely to achieve clinical benefit from resulting product candidates.

On June 4, 2024 Personalis, Inc. (Nasdaq: PSNL) reported that data presented at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) oral podium talks in Chicago, IL demonstrated that the Personalis NeXT Personal test had exceptional detection rates and performance for early-stage breast cancer and immunotherapy monitoring (Press release, Personalis, JUN 4, 2024, View Source [SID1234644105]). The NeXT Personal test is the first of a new class of ultra-sensitive liquid biopsy tests designed to detect the earliest traces of cancer recurrence and monitor a patient’s response to therapy. The test can detect circulating tumor DNA (ctDNA) down to an ultra-sensitive range (<100 parts per million of ctDNA) and the data presented as ASCO (Free ASCO Whitepaper) highlights the clinical importance of this approach.

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Earlier and more sensitive detection of recurrence in early-stage breast cancer

Breast cancer is currently the most common cancer in the U.S., with an estimated 300,000 new cases and approximately 40,000 deaths forecasted for 2024 according to the U.S. National Cancer Institute (NCI). The current standard of care for relapse detection of breast cancer is primarily imaging such as mammography, which can have limited sensitivity. These studies are focused on addressing this challenge through advanced ctDNA analysis with NeXT Personal.

Breast cancer results were presented in an oral presentation by Dr. Isaac Garcia-Murillas and come from a team at the Institute of Cancer Research, London and Royal Marsden NHS Foundation Trust in the UK led by Professor Nicholas Turner, renowned for his work on the use of ctDNA to guide breast cancer treatment. In this study, they found:

NeXT Personal’s Ultra-sensitive range enabled earlier detection of recurrence, with a median ~15-month lead time over imaging detection
100% of patients that recurred were detected with NeXT Personal and 100% of patients that were ctDNA negative on longitudinal testing were cancer-free
NeXT Personal enabled detection of very low traces of cancer, with ~39% of all detections falling in the ultra-sensitive range below 100 PPM (below 0.01% of ctDNA)
NeXT Personal enabled substantially better sensitivity and lead times compared to other MRD assays on the same patient cohort
Dr. Garcia-Murillas noted, "NeXT Personal demonstrated the best MRD performance we have seen in this study cohort. With the ultra-sensitive performance of NeXT Personal, we see strong opportunities to impact breast cancer care and management, especially for the escalation and de-escalation of treatment."

Additional breast cancer results presented at ASCO (Free ASCO Whitepaper) include a poster presentation by Dr. Adrienne Waks at the Dana Farber Cancer Institute using NeXT Personal to assess neoadjuvant therapy response in the DAPHNe HER2+ breast cancer trial. In this study, NeXT Personal demonstrated high baseline sensitivity (92%) for ctDNA for HER2+ breast cancer patients enabled by the ultra-sensitivity of the test with 27% of detections in the ultra-sensitive range. NeXT Personal was also able to demonstrate neoadjuvant THP treatment effectiveness by showing the treatment had cleared the tumor MRD.

Strong performance in immunotherapy monitoring

Several hundred thousand cancer patients are put on immunotherapy treatment annually. While over 40% of patients with cancer are eligible for immunotherapy, only ~12% of patients respond, underscoring the need for a blood test that monitors treatment response for patients, doctors, and payers.

An oral presentation showed the importance of NeXT Personal’s use for immunotherapy monitoring. Dr. Rodrigo Toledo at the Vall d’Hebron Institute of Oncology (VHIO) presented data in an oral presentation that demonstrated that the baseline levels and the changes in levels of ctDNA detected by NeXT Personal are highly predictive of therapy response and clinical outcomes for late-stage cancer patients receiving immunotherapy. This includes the finding that patients who had a significant decrease in ctDNA levels from baseline to the third cycle of immunotherapy had overall survival that was more than two times longer than those who did not. They also demonstrated that NeXT Personal had an average lead time for detecting progression of 81 days over imaging.

The VHIO data is a broad study that included patients across 18 different solid tumor types. "The changes in ctDNA levels elucidated by the NeXT Personal test can dramatically enhance our ability to understand if late-stage cancer patients are responding to their therapy. This is critical to optimally managing immunotherapy and other treatments for these very sick patients," said Dr. Toledo.

Additional results presented at ASCO (Free ASCO Whitepaper) include a poster presentation by Professor Andy Nixon at the Duke Cancer Institute in late-stage esophagogastric cancer that received immunotherapy in combination with chemotherapy as part of the KeyLargo trial. In this study, Dr. Nixon found that ctDNA levels were demonstrated to be highly prognostic for therapy response. In late-stage cancer patients, ctDNA levels can be very low with ~20% of samples falling in the ultra-sensitive range, underscoring the importance of an ultra-sensitive test like NeXT Personal.

"With the addition of the ASCO (Free ASCO Whitepaper) data, we now have presented data across lung cancer, breast cancer, and patients on immunotherapy that consistently highlight the importance of an ultra-sensitive MRD platform like NeXT Personal to detect recurrence earlier, monitor therapy response, and more accurately predict clinical outcomes for cancer patients," said Dr. Richard Chen, Chief Medical Officer and EVP of R&D at Personalis. "We also expect the strong performance in these studies will help drive clinical adoption and reimbursement of NeXT Personal."

Personalis will host a webinar call on June 19th, 2024 at 1:00 p.m. Pacific Time / 4:00 p.m. Eastern Time to present ASCO (Free ASCO Whitepaper) highlights from the conference.

Webcast and Conference Call Information

To receive the dial-in instructions, please email [email protected].

On June 4, 2024 AbelZeta Pharma, Inc. ("AbelZeta" or the "Company"), a global clinical-stage biopharmaceutical company focused on the discovery and development of innovative and proprietary cell-based therapeutic products, reported preliminary safety and efficacy results from its first time in human investigator-initiated trial (IIT) of C-CAR031 in connection with the Company’s oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, AbelZeta, JUN 4, 2024, View Source [SID1234644103]). The presentation shared data indicating a manageable safety profile and encouraging anti-tumor activity of C-CAR031 in patients with heavily pretreated advanced hepatocellular carcinoma (HCC) (1-6 lines of prior therapy). C-CAR031 is based on a novel GPC3-targeting CAR-T designed by AstraZeneca (LSE/STO/Nasdaq: AZN) and is manufactured by AbelZeta. C-CAR031 is being co-developed in China by AbelZeta and AstraZeneca.

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"We are encouraged by the first clinical results of C-CAR031 in advanced hepatocellular carcinoma (HCC) patients," said Tony (Bizuo) Liu, Chairman and CEO of AbelZeta. "The early data presented today provide compelling proof-of-concept to potentially redefine therapeutic paradigms in HCC and other GPC3-expressing solid tumors."

Principal Investigator (PI) of the study, Professor Tingbo Liang from the First Affiliated Hospital of Zhejiang University, stated "C-CAR031 showed a good safety profile and promising efficacy in late-stage hepatocellular carcinoma patients, who typically have a limited number of treatment options available. The observed tumor shrinkage in the large/vast majority (91.3%) of the patients suggests that C-CAR031 has the potential to bring clinical value and offer hope to these patients."

As of March 14, 2024, 23 of 24 patients on the study were eligible for efficacy assessment. Tumor reductions were observed in 91.3% patients, in both intrahepatic and extrahepatic lesions, with a median reduction of 42.2% (range, -28.1% 94.4%). The disease control rate was 91.3% and the ORR was 56.5% for patients across all DLs. In DL4, the ORR was 75.0%. With 9.03-month median follow-up, Kaplan-Meier estimation of median overall survival (mOS) is 11.14 months (95% CI, 7.56-NE).

No dose-limiting toxicity or immune effector cell associated neurotoxicity syndrome (ICANS) was observed. Cytokine release syndrome (CRS) was observed in 22 (91.7%) patients with the majority (87.5%) grade 1/2 CRS and only 1 (4.2%) grade 3 CRS.

About C-CAR031

C-CAR031 is an autologous, armored GPC3-targeting chimeric antigen receptor T-Cell (CAR-T) therapy, being studied for the treatment of HCC. It is based on a novel GPC3-targeting CAR-T designed by AstraZeneca using their dominant negative transforming growth factor-beta receptor II dominant negative (dnTGFβRII) armoring discovery platform and is manufactured by AbelZeta in China. C-CAR031 is being developed in China under a co-development agreement between AbelZeta and AstraZeneca.1

About the Study

A Phase I clinical study (NCT05155189) aiming to assess the safety and anti-tumor activity of C-CAR031 injection in advanced/unresectable HCC patients is being conducted in China. As of March 14, 2024, a total of 24 patients received C-CAR031 infusion at 4 dose levels (DLs). 83.3% (20/24) had extrahepatic metastasis. The median number of prior lines of systemic therapy was 3.5 (range 1-6).

Abstract Title: "Phase I study of C-CAR031, a GPC3-specific TGFβRIIDN armored autologous CAR-T, in patients with advanced hepatocellular carcinoma (HCC)."
Abstract Number: 4019
Session Type and Title: Rapid Oral Abstract – Gastrointestinal Cancer – Gastroesophageal, Pancreatic, and Hepatobiliary
Session Date and Time: 6/3/2024; 9:45 AM-11:15 AM CDT

On June 4, 2024 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, reported that the final follow-up results of the investigator-initiated trial CT041-CG4006 (NCT03874897) of satricabtagene autoleucel ("satri-cel", CT041) (an autologous CAR T-cell product candidate against Claudin18.2) have been published in Nature Medicine on June 3, 2024. Data were presented as an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ("ASCO") Annual Meeting on June 3, 2024, 12:30 pm-3:30 pm, Eastern Daylight Time (Press release, Carsgen Therapeutics, JUN 4, 2024, View Source [SID1234644102]). Further details have been posted on the corporate website View Source

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The article in Nature Medicine was titled "Claudin18.2-specific CAR T Cells in gastrointestinal cancers: phase 1 trial final results".[1]

The 2024 ASCO (Free ASCO Whitepaper) Annual Meeting abstract was titled "Claudin18.2-Targeted Chimeric Antigen Receptor T Cell Therapy for Patients with Gastrointestinal Cancers: Final Results of CT041-CG4006 Phase 1 Trial".[2]

The leading PI of this study, Professor Lin Shen of Beijing Cancer Hospital, said, "Satri-cel has shown promising efficacy and manageable safety profiles in patients with Claudin18.2-positive advanced gastrointestinal cancers, particularly those with gastric cancer or gastroesophageal junction cancer. This study marks a significant advancement in the field of CAR T-cell therapy for solid tumors. It suggests that CAR T-cell therapy has the potential to transform existing treatment paradigms and provides important reference points for further innovative research. In the future, we anticipate that more clinical trials and studies will further validate and refine this innovative therapy, enabling it to benefit a broader patient population as soon as possible."

Dr. Zonghai Li, Founder, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics, said, "We are delighted to announce that the final results of the CT041-CG4006 study have been simultaneously published in the prestigious journal Nature Medicine and reported as an oral presentation at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting. This study represents a significant milestone in the field of CAR T-cell therapy for solid tumors, demonstrating the encouraging safety and efficacy of satri-cel. We extend our heartfelt thanks to the investigators for their years of dedicated efforts, and to the patients and their families for their trust and support. It is our shared goal to provide better treatment options for patients, and we will continue to advance the global clinical development of satri-cel, ensuring this innovative CAR T-cell therapy benefits more patients with gastric, pancreatic, and other gastrointestinal cancers."

About Satri-cel

Satri-cel is an autologous CAR T-cell product candidate against the protein Claudin18.2 that can potentially be the first-in-class globally. Satri-cel has been developed for the treatment of Claudin18.2 positive solid tumors with a primary focus on gastric cancer/gastroesophageal junction cancer (GC/GEJ) and pancreatic cancer (PC). Ongoing trials include investigator-initiated trials (CT041-CG4006, NCT03874897), a confirmatory Phase II clinical trial for advanced GC/GEJ in China (CT041-ST-01, NCT04581473), a Phase I clinical trial for PC adjuvant therapy in China (CT041-ST-05, NCT05911217), and a Phase 1b/2 clinical trial for advanced gastric or pancreatic adenocarcinoma in North America (CT041-ST-02, NCT04404595). Satri-cel was granted Regenerative Medicine Advanced Therapy (RMAT) designation by the U.S. FDA for the treatment of advanced GC/GEJ with Claudin18.2-positive tumors in January 2022 and was granted PRIME eligibility by the EMA for the treatment of advanced gastric cancer in November 2021. Satri-cel received an Orphan Drug designation from the U.S. FDA in 2020 for the treatment of GC/GEJ and an Orphan Medicinal Product designation from the EMA in 2021 for the treatment of advanced gastric cancer.

On June 4, 2024 SciTech Development, a clinical-stage, specialty oncology pharmaceutical company, reported it has closed an additional $3.2 million in funding to continue the active enrollment and dosing of patients in its ongoing clinical trial for T-cell non-Hodgkin lymphoma (T-NHL) (Press release, SciTech Development, JUN 4, 2024, View Source [SID1234644101]).

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This new funding brings SciTech’s total raised to over $12 million. SciTech’s financing was led by Storm Lake Capital and Pointe Angels, alongside new and existing accredited investors. Proceeds from the financing will be used to advance the company’s Phase 1b clinical trials of ST-001 for T-NHL and subsequent clinical trials for small cell lung cancer.

"On behalf of Storm Lake Capital, we are thrilled with the initial clinical progress made by SciTech Development and pleased to further support the company through additional investment in its latest convertible note round." said Todd Carlson, Partner, Storm Lake Capital. "As early supporters, we have closely monitored SciTech’s advancements, noting its adept handling of challenges and disciplined resource management. We value the management team’s integrity and look forward to their continued success."

SciTech’s T-NHL trial began with the first patient dosed in late 2023 and is being conducted at six (6) prestigious cancer institutions located across the United States in PA, NY, TX, MI, and CA, with additional sites being added. Patient enrollment is now open. Trial information, including criteria and site locations, can be found at ClinicalTrials.gov with the identifier NCT04234048. SciTech anticipates starting a second Phase 1b small cell lung cancer (SCLC) trial to run concurrently with the T-cell lymphoma trial.

"SciTech has achieved yet another milestone of having oversubscribed its second Convertible Note Round (CNR) of financing. This is a perfect reflection of the progress that has been made by our dedicated team. Our multicenter clinical trial is to reconfirm the safety and efficacy of the active drug, fenretinide, utilizing SciTech’s novel nanoparticle delivery platform." said Earle Holsapple, CEO of SciTech. "We have opened a third CNR to continue advancing the Phase 1b studies for T-NHL and small cell lung cancer. In parallel, the company will launch a Series A capital raise to fund the completion of both trials and file for commercial approval with the FDA. We are confident that the drug’s potential will soon be realized."

ST-001 is SciTech’s patented lead drug product, formulated with the active drug fenretinide (a synthetic retinoid derivative) plus specific phospholipids in a nanoparticalized delivery platform (SDP). ST-001 has achieved a breakthrough in solving the bioavailability issues of fenretinide without system-related toxicities, which allows the drug to reach and kill cancer cells. The FDA has granted ST-001 an Orphan Drug Designation, allowing 7 years of market exclusivity once approved.

T-cell lymphoma, a rare disease, is being utilized as the initial gateway indication for ST-001 as the company plans to establish a foothold in other cancer indications. Previous studies with fenretinide have shown promise in at least 15+ other types of cancers, such as lung, breast, ovarian, cervical, pancreatic, leukemia, colo-rectal, head & neck, and brain cancers. These additional indications, plus the potential to add ST-001 as combination therapy, may add significant value to address the unmet clinical needs in oncology.