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- Confirmed partial responses (PRs) doubled to four since ASCO GI in MSS CRC patients without liver and peritoneal metastases for overall response rate (ORR) of 24% (4/17) with ADG126 10 mg/kg every three weeks (Q3W) in combination with pembrolizumab - - Median progression-free survival of 8.5 months observed in patients without liver and peritoneal metastases at the ADG126 10 mg/kg Q3W dose - - At the 10 mg/kg dose level, 12-month overall survival (OS) rates were 74% for patients without liver metastases, and 82% for those without liver and peritoneal metastases - - Safety profile maintained, with only 16% Grade 3 TRAEs in patients treated with ADG126 10 mg/kg Q3W in combination with pembrolizumab - - Combination shows potential with standard of care to address broader patient populations, including MSS CRC patients with liver metastases - Sept. 16, 2024 -- Adagene Inc. (“Adagene”) (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, today announced new ADG126 clinical data presented at the ESMO Congress, taking place in Barcelona, Spain, September 13-17. The poster, titled Increased Therapeutic Index of Muzastotug (ADG126), a Masked Anti-CTLA-4 Antibody, in Combination with Pembrolizumab (Pembro) Enables Significant Clinical Benefits and Supports Further Clinical Development in Patients with Metastatic MSS CRC, reports data from an ongoing phase 1b/2 trial of Adagene’s masked anti-CTLA-4 SAFEbody in combination with Merck & Co., Inc., Rahway, NJ, USA's anti-PD-1 therapy KEYTRUDA® (pembrolizumab) (ADG126-P001; NCT05405595). “I am delighted that the ESMO data show a promising overall response rate, progression-free survival (PFS) and early survival benefit from treatment with the immunotherapy (IO) doublet of ADG126 in combination with pembrolizumab for patients with advanced/metastatic MSS CRC, the largest segment of colorectal cancer with few treatment options,” said Daneng Li, MD, Associate Professor in the Department of Medical Oncology & Therapeutics Research at the City of Hope Comprehensive Cancer Center, and a study investigator. “With a much higher dosing level than available anti-CTLA-4 therapies, these data reinforce the encouraging safety and efficacy profile for ADG126 administered repeatedly in MSS CRC.” Dr. Li continued, “Given the best-in-class potential for ADG126, this combination with pembrolizumab could address even broader patient populations, such as those with liver metastases, particularly if combined with standard of care to control early disease progression. Further, the safety profile of this immunotherapy doublet enables repeat cycles to achieve and sustain sufficient drug exposure that maximizes potential for a long-term survival benefit.” ADG126 is a masked anti-CTLA-4 SAFEbody targeting a unique epitope of CTLA-4 on regulatory T cells (Tregs) in tumor tissue which shows potential best-in-class safety and efficacy profiles in combination with pembrolizumab. The unique epitope of ADG126 alone has shown enhanced antibody-dependent cell mediated cytotoxicity without Fc engineering, which is associated with significantly increased toxicity. Further, it has shown minimal immunogenicity and anti-drug antibodies, with no impact on its pharmacokinetic (PK) profile. ADG126 in combination with pembrolizumab continued to demonstrate a differentiated safety profile in dose escalation and dose expansion cohorts for heavily pre-treated advanced/metastatic patients with solid tumors (n=66): No dose-limiting toxicities (DLT) or Grade 4 or 5 TRAEs were observed at any dose up to 20 mg/kg Q3W, which was evaluated in dose escalation (n=6) to support an ongoing loading dose cohort. No Grade 3 colitis was observed at any dose, with limited use of infliximab to manage immune-mediated diarrhea/colitis in no more than 10% of patients. No significant late-onset toxicities were observed after repeat dosing at the 10 mg/kg dose level. TRAEs by week from treatment start are summarized in the poster. Grade 3 TRAEs occurred in only 6% of patients at the 10 mg/kg Q6W dose (1/17) and 16% of patients at the 10 mg/kg Q3W dose (6/37). Standard of care treatments are associated with higher rates of toxicities. Seven patients developed treatment related SAEs; however, the discontinuation rate remains low at 8% (5/66).​ ADG126 administered at 10 mg/kg Q6W or Q3W in combination with pembrolizumab (200 mg/Q3W) demonstrated an encouraging efficacy signal, durable disease control and an early survival benefit in MSS CRC patients, with dose-dependent efficacy and objective responses per RECIST criteria observed for the Q3W schedule: In the subset of efficacy evaluable patients without liver and peritoneal metastases (n=17) who received ADG126 10 mg/kg Q3W, an ORR of 24% was observed, including four confirmed PRs. These results are consistent with earlier ORR data published at ASCO GI 2024. Response rates for current standard of care treatments range from 1% to 6.3%*. An additional 11 patients had stable disease (SD) for an overall disease control rate (DCR) of 88% (15/17). Further, a median PFS of 8.5 months was observed in the subset at the ADG126 10 mg/kg Q3W dose and median PFS was 5.9 months for patients at the ADG126 10 mg/kg Q6W dose. The 12-month OS rates were 74% for those patients without liver metastases (n=36), and 82% in those without liver and peritoneal metastases (n=24) in the combined 10 mg/kg Q6W and Q3W cohorts.​​ While the 10 mg/kg Q3W cohort demonstrated efficacy with RECIST responses and the Q6W did not, early OS rates appear comparable for both doses. This suggests that the Q6W could be used as a starting point for future combination trials, or as a dose modification strategy for safety management. Additionally, results in patients without liver metastases who received at least four cycles of the combination showed comparable OS rates to those without liver and peritoneal metastases, highlighting the importance of early disease control with standard of care to enable the IO doublet to drive a long-term survival benefit. In dose escalation, the 20 mg/kg Q3W dose level was tolerable for the initial cycle (n=6). Based upon the safety profile of the initial dose, 20 mg/kg is being evaluated as a loading dose in an expansion cohort that has enrolled 12 patients. This cohort is evaluating a single dose of ADG126 at 20 mg/kg followed by a 10 mg/kg Q3W maintenance dose in combination with pembrolizumab. Initial data for this cohort are expected later this year. Comprehensive PK and exposure response analyses were also conducted to provide insight on various dosing regimens and their correlation to safety and efficacy of the combination. These results reinforce the increased therapeutic index of ADG126, underscoring a key advantage of the SAFEbody® precision masking technology. The extensive PK data also guide future clinical development and dose selection to meet FDA’s Project Optimus dose optimization requirements. Commenting on these promising results, Peter Luo, Adagene’s CEO and President of R&D said, “We are thrilled that today’s update continues to reinforce the clinical benefits of the best-in-class therapeutic potential for ADG126 at the 10 mg/kg dose level in combination with pembrolizumab in MSS CRC. Armed with these results and the anticipated findings from our ongoing 20 mg/kg loading dose regimen, we are moving ahead with plans to evaluate ADG126 in MSS CRC at 10- to 20-fold higher doses than ipilimumab in a randomized, registration-oriented clinical program. With safety comparable to historical data for pembrolizumab monotherapy, these data provide a solid foundation for the potential of an IO doublet targeting CTLA-4 and PD-1 to move into earlier lines of therapy and broader patient populations, particularly when combined with standard of care aiming for a transformational improvement in patient outcomes.” KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. SAFEbody® is a registered trademark in the United States, China, Australia, Japan, Singapore, and the European Union. *Grothey et al. Lancet. 2013;381: 303-312; FDA label, 12/10/2020. Mayer et al. N Eng J Med. 2015;372: 1909-1919. Marcus et al. Clin Cancer Res; 23(12) June 15, 2017;2924-2927. Josep Tabernero et al. 2023 ASCO Gastrointestinal. Gerald W. Prager et al. N Engl J Med 2023 May 04;388(18). Shukui Qin et al. 2019 CSCO. Jin Li et al. JAMA. 2018;319(24): 2486-2496. Andrea J. Bullock et al. 2023 ESMO-GI. Anthony B et al. 2023 ASCO-GI. Elena et al. 2021 ASCO. E. Garralda et al. 2022 ESMO. Adagene Inc. (Nasdaq: ADAG) is a platform-driven, clinical-stage biotechnology company committed to transforming the discovery and development of novel antibody-based cancer immunotherapies. Adagene combines computational biology and artificial intelligence to design novel antibodies that address globally unmet patient needs. The company has forged strategic collaborations with reputable global partners that leverage its SAFEbody® precision masking technology in multiple approaches at the vanguard of science. Powered by its proprietary Dynamic Precision Library (DPL) platform, composed of NEObody™, SAFEbody, and POWERbody™ technologies, Adagene’s highly differentiated pipeline features novel immunotherapy programs. The company’s SAFEbody technology is designed to address safety and tolerability challenges associated with many antibody therapeutics by using precision masking technology to shield the binding domain of the biologic therapy. Through activation in the tumor microenvironment, this allows for tumor-specific targeting of antibodies in tumor microenvironment, while minimizing on-target off-tumor toxicity in healthy tissues. Adagene’s lead clinical program, ADG126 (Muzastotug), is a masked, anti-CTLA-4 SAFEbody that targets a unique epitope of CTLA-4 in regulatory T cells (Tregs) in the tumor microenvironment. ADG126 is currently in phase 1b/2 clinical studies in combination with anti-PD-1 therapy, particularly focused on Metastatic Microsatellite-stable (MSS) Colorectal Cancer (CRC). Validated by ongoing clinical research, the SAFEbody platform can be applied to a wide variety of antibody-based therapeutic modalities, including Fc empowered antibodies, antibody-drug conjugates, and bi/multispecific T-cell engagers. The content above comes from the network. if any infringement, please contact us to modify.

A Phase IIb trial is assessing the safety and efficacy of the asset in patients with ovarian cancer-derived peritoneal metastases. Credit: Tattoboo/ Shutterstock. Oncoinvent has received fast-track designation from the US Food and Drug Administration (FDA) for its therapy, Radspherin, to treat peritoneal metastases from ovarian cancer. The process expedites the development and review of products targeting serious conditions with unmet medical needs, potentially enabling earlier patient access to new medicines. Fast-track status will offer Oncoinvent the advantage of more frequent interactions with the FDA throughout the clinical development of Radspherin. The designation makes it a candidate for accelerated approval and priority review. A lead candidate of the company, Radspherin is currently being evaluated in two active clinical studies for the treatment of peritoneal carcinomatosis resulting from both ovarian and colorectal cancer. See Also: Pharma M&A: The top high value deals in 2023 Medical packaging companies in pharmaceutical contract manufacturing An ongoing controlled, randomised Phase IIb clinical trial is assessing the safety and efficacy of Radspherin in patients with ovarian cancer-derived peritoneal metastases. The trial’s primary goal is to compare progression-free survival rates between patients receiving Radspherin post-surgical resection after pre-operative chemotherapy and those who receive the chemotherapy and surgery alone. Interim analysis from the Phase I/IIa safety study demonstrated promising results, with Radspherin offering a good tolerability profile. No dose-limiting toxicity was seen at the recommended 7MBq dose. Oncoinvent CEO Anders Månsson stated: “Fast track designation for Radspherin is a key milestone for Oncoinvent, particularly as we are on the verge of initiating a Phase IIb trial to evaluate Radspherin in peritoneal metastases from ovarian cancer, and later also in peritoneal metastases stemming from colorectal cancer patients. “We believe we are well positioned to execute the clinical development of Radspherin in our upcoming trial and look forward to advancing this innovative product candidate to benefit patients battling this type of cancer, for whom there are limited treatment options.”

[12-October-2023] SHANGHAI, Oct. 12, 2023 /PRNewswire/ -- 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, announced the publication of two cases of long-term disease-free survival in the treatment of advanced hepatocellular carcinoma (HCC) with CARsgen's innovative CAR-GPC3 T-cell therapy. These results were recently published in Cancer Communications as the cover story, titled "Combined local therapy and CAR-GPC3 T-cell therapy in advanced hepatocellular carcinoma: a proof-of-concept treatment strategy" （ ）[1]. Hepatocellular carcinoma is one of the most common malignant tumors, with approximately 780,000 annual incidence cases globally. There is an urgent need for new therapeutic techniques and strategies to improve the prognosis of these patients. Recurrence and metastasis are the primary factors impacting HCC patients' lives. For HCC patients with concurrent inferior vena cava tumor thrombus, treatment options are limited, and overall prognosis is poor. Even with surgical resection, the median overall survival is only 17.8 months postoperatively [2]. For those undergoing other local or systemic treatments, the median overall survival ranges from 5.9 to 15.4 months [2-4]. In May 2015, the Department of Interventional Oncology of Renji Hospital in Shanghai collaborated with CARsgen Therapeutics to initiate the first clinical study with CAR T-cell therapy targeting the GPC3 (Glypican-3) protein in advanced hepatocellular carcinoma. (Partial data from this study was published in Clin Cancer Res. 2020[5]). At the time of enrollment, two patients already presented inferior vena cava tumor thrombus, and one of them also had retroperitoneal lymph node metastasis, a particularly poor prognosis factor for the outcome. However, both patients maintained a tumor-free status during long-term follow-up after receiving a combination of local and CAR T-cell therapies. Recently, the two patients returned to Renji Hospital for a follow-up examination, which confirmed the absence of tumor recurrence. Researchers at Renji Hospital held a brief celebration event together with these two patients. Patient 1, upon confirmed diagnosis of liver cancer, underwent two rounds of interventional therapy and one session of microwave ablation. However, his disease rapidly progressed and he developed an inferior vena cava tumor thrombus. Following localized treatments (microwave ablation and gamma knife) targeting intrahepatic recurrent tumors and the inferior vena cava tumor thrombus, the patient was enrolled in the CAR-GPC3 T-cell clinical trial. Six months later, tumor biomarkers AFP returned to normal, and imaging showed no evident active tumors. To date, the patient has remained tumor-free for over 8 years (July 2015 to August 2023). Patient 2, following liver cancer resection, experienced intrahepatic tumor recurrence. Despite multiple intensive sessions of TACE and microwave ablation, the tumor could not be effectively controlled. Multiple recurrences (greater than 6 lesions) appeared within the liver, and the patient developed retroperitoneal lymph node metastasis and inferior vena cava tumor thrombus. Through localized treatments (microwave ablation and gamma knife) addressing intrahepatic tumors, the inferior vena cava tumor thrombus, and peritoneal lymph node metastases, combined with CAR T-cell therapy, the patient has currently achieved over 7 years of tumor-free survival (July 2016 to August 2023). Meanwhile, pyrexia, fatigue, transient leukopenia, thrombocytopenia, and grade 1 cytokine release syndrome were reported during CAR-GPC3 T-cell infusions in this patient. Throughout the follow-up period, both patients only received oral anti-hepatitis B virus medication, with no other cancer treatments administered. Professor Bo Zhai, the principal investigator of this study and the Director of the Department of Interventional Oncology of Renji Hospital, Shanghai Jiao Tong University School of Medicine, said, "The treatment of advanced hepatocellular carcinoma has always been a great challenge, particularly for patients with inferior vena cava tumor thrombus, a poor prognosis factor. In this case report, two patients achieved long-term tumor-free survival through a combination of localized treatment and CAR T-cell therapy targeting GPC3, offering new hope for advanced hepatocellular carcinoma patients. Despite the tremendous efforts of scientists, the development of CAR T-cell therapy for solid tumors still encounter various challenges, such as the inherent physical and immune barriers of solid tumors, tumor cell heterogeneity, antigen specificity, and the potential risks associated with CAR T-cell therapy." Dr. Zonghai Li, Founder, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen, added, "With the mission of making cancer curable, CARsgen has been developing various innovative strategies for the treatment of solid tumors using CAR-T cells. For example, we firstly reported the combination of small-molecule drugs with CAR-GPC3 T-cell therapy to achieve sustained complete response in a subject with advanced hepatocellular carcinoma [6]. This time, after receiving local therapy and targeted CAR-GPC3 T-cell infusion, two patients with advanced hepatocellular carcinoma reported in the study have achieved disease-free survival for more than seven years, demonstrating that CAR T-cell therapies have the potential to cure solid tumors through innovative treatment strategies." About CARsgen Therapeutics Holdings Limited CARsgen is a biopharmaceutical company with operations in China and the U.S. and is focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors. CARsgen has established a comprehensive CAR T-cell research and development platform, encompassing target discovery, innovative CAR T-cell development, clinical trials, and commercial-scale production. CARsgen has internally developed novel technologies and a product pipeline with global rights to address major challenges of CAR T-cell therapies, such as improving the safety profile, enhancing the efficacy in treating solid tumors, and reducing treatment costs. CARsgen's vision is to become a global biopharmaceutical leader that brings innovative and differentiated cell therapies to cancer patients worldwide and makes cancer curable. Forward-looking Statements All statements in this press release that are not historical fact or that do not relate to present facts or current conditions are forward-looking statements. Such forward-looking statements express the Group's current views, projections, beliefs and expectations with respect to future events as of the date of this press release. Such forward-looking statements are based on a number of assumptions and factors beyond the Group's control. As a result, they are subject to significant risks and uncertainties, and actual events or results may differ materially from these forward-looking statements and the forward-looking events discussed in this press release might not occur. Such risks and uncertainties include, but are not limited to, those detailed under the heading "Principal Risks and Uncertainties" in our most recent annual report and interim report and other announcements and reports made available on our corporate website, . No representation or warranty is given as to the achievement or reasonableness of, and no reliance should be placed on, any projections, targets, estimates or forecasts contained in this press release. References Shi Y, et. al. Cancer Commun (Lond). 2023 Jul 21. Kokudo T, et. al. Hepatology. 2017 Aug; 66(2):510-517. Lou J, et. al. BMC Cancer. 2019 Jul 5;19(1):668. Rim CH, et. al. Int J Radiat Biol. 2020 Jun; 96(6):759-766. Shi DH, et al. Clin Cancer Res. 2020; 26(15):3979-3989. Sun H, et. al. Front Immunol. 2022 Aug 17;13:963031. Contact CARsgen For more information, please visit Public Relations: PR@carsgen.com Investor Relations: IR@carsgen.com Company Codes: HongKong:2171