Secondary malignant neoplasm of peritoneum

OSLO, Norway--( BUSINESS WIRE )--Oncoinvent ASA, a clinical stage company advancing alpha emitter therapy across a variety of solid cancers, today announced an interim data readout of the Phase 1/2a studies of Radspherin® for the treatment of peritoneal carcinomatoses. The studies were closed for recruitment at the end of 2023, and patients are currently in long-term follow-up. The readout confirmed the previously published results on efficacy and adds further confidence in the ongoing randomized controlled Phase 2 clinical trial for Radspherin® in patients with ovarian cancer. In the first interim readout from the Phase 1 study in ovarian cancer, only 1 patient out of the 10 receiving the selected dose (10%) had peritoneal recurrence at the 12-month interim readout, compared to an expected recurrence rate of 25% in similar populations [1-3]. Correspondingly, in the second intermediate readout of the colorectal cancer study, only 3 of 20 patients (15%) receiving the selected dose of 7 MBq had peritoneal recurrence after the full 18 months follow-up period. With current standard therapy, the expected peritoneal recurrence rate is approximately 50% after 18 months [4]. 36 patients with colorectal cancer have received the selected dose, with results from the final 16 patients still pending full follow-up. “We are excited to announce the interim results of our Phase1/2a studies of Radspherin®, confirming a positive efficacy signal and demonstrating Radspherin’s® ability to enable local control in the peritoneum, thus ensuring patients remain in remission after surgery,” said Oystein Soug, Chief Executive Officer of Oncoinvent. “These positive results increase confidence in the further development of Radspherin® as an effective treatment option for patients suffering from peritoneal carcinomatoses, a condition that is notoriously difficult to treat effectively with systemic therapy.” “Patients with ovarian cancer often have peritoneal carcinomatoses already at diagnosis, giving them higher recurrence rate and worse prognosis - so an effective treatment targeted specifically at these carcinomatoses could reduce recurrence and prolong survival,” says Yun Wang, MD PhD, Department of Gynecologic Oncology, The Norwegian Radium Hospital, Oslo University Hospital, principal investigator in the RAD-18-001 study. About Radspherin Radspherin® is an investigational radiopharmaceutical designed for the local treatment of cancer that has spread to body cavities. It consists of billions of calcium carbonate microparticles containing the radioactive material radium-224. The mode of action is the decay of radium-224 emitting alpha-particles, a highly potent form of ionizing radiation. Radspherin® is investigated in ongoing clinical studies to treat peritoneal carcinomatoses from ovarian and colorectal cancer and it is administered intraperitoneally after surgical resection with removal of all macroscopic tumors. About the RAD-18-001 and RAD-18-002 study Two early phase studies with Radspherin® in patients with peritoneal carcinomatoses have completed recruitment at the end of 2023 with 68 patients treated. One study in patients with peritoneal carcinomatoses from platinum sensitive recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma (RAD-18-001, n=21, phase 1) scheduled for secondary cytoreduction, and one in patients with peritoneal carcinomatoses from colorectal cancer (RAD-18-002, n=47, phase 1/2a) scheduled for cytoreduction and HIPEC. The two studies were designed to evaluate the dose, safety and tolerability, dosimetry, and signal of efficacy of Radspherin®. About Oncoinvent Oncoinvent ASA is a clinical stage, radiopharmaceutical company developing innovative treatments for solid cancers. The technology platform is focused on the use of alpha-emitting radionuclides to deliver powerful radiation directly to cancer cells. The Company’s lead product candidate, Radspherin®, is being advanced through clinical development by a team with experience from all stages of radiopharmaceutical development. Internal manufacturing and supply chain capabilities have been established, which now have the capacity to supply Radspherin® for multi-center phase 2 clinical studies. Forward-Looking Statements All statements other than statements of historical facts contained in this press release are forward-looking statements and are not a representation that Oncoinvent’s plans, estimates, or expectations will be achieved. These forward-looking statements represent Oncoinvent’s expectations as of the date of this press release, and Oncoinvent disclaims any obligation to update the forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to whether the results of clinical or other studies will support the use of our product offerings, the impact of results of such studies, our expectations of the reliability, accuracy and performance of our tests, or of the benefits of our tests and product offerings to patients, providers and payers. References [1] Coleman, R. L., Spirtos, N. M., Enserro, D., Herzog, T. J., Sabbatini, P., Armstrong, D. K., ... & Mannel, R. S. (2019). Secondary surgical cytoreduction for recurrent ovarian cancer. New England Journal of Medicine , 381 (20), 1929-1939. [2] Harter, P., Sehouli, J., Vergote, I., Ferron, G., Reuss, A., Meier, W., ... & Du Bois, A. (2021). Randomized trial of cytoreductive surgery for relapsed ovarian cancer. New England Journal of Medicine , 385 (23), 2123-2131. [3] Shi, T., Zhu, J., Feng, Y., Tu, D., Zhang, Y., Zhang, P., ... & Zang, R. (2021). Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial. The Lancet Oncology , 22 (4), 439-449. [4] Quénet, F., Elias, D., Roca, L., Goéré, D., Ghouti, L., Pocard, M., ... & Patrick, R. A. T. (2021). Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial. The Lancet Oncology , 22 (2), 256-266.

OSLO, Norway--( BUSINESS WIRE )--Oncoinvent AS, a clinical stage company advancing alpha emitter therapy across a variety of solid cancers, today announced the publication of data from the Phase 1/2a study of Radspherin® in colorectal cancer patients in the peer-reviewed Journal of Surgical Oncology . The results, previously presented at the 2023 Peritoneal Surface Oncology Group International (PSOGI) Congress in Venice, show encouraging 18 months safety and efficacy data from the 23 patients enrolled in the Phase 1 part of the RAD-18-002 study in colorectal cancer patients. “We are pleased to see our data published in such a well-recognized scientific journal,” commented Professor Emeritus Oyvind Bruland, MD, PhD, senior author on the manuscript, co-founder and member of Oncoinvent’s scientific advisory board. "The data in the publication highlights the potential of Radspherin® in treating patients with peritoneal metastases from colorectal cancer, a condition for which there is an urgent unmet need for novel treatment options." “Patients with liver and lung metastases benefit considerably from several other new treatment options, but not those with peritoneal metastases,” commented Stein G. Larsen, MD, PhD, principal investigator of the study and chief gastrosurgeon, the Norwegian Radium Hospital, Oslo University Hospital. The publication concludes that Radspherin® was well tolerated following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). At 18 months, none of the patients receiving the recommended dose (7 MBq) had peritoneal recurrences. Radspherin® also showed a promising signal of efficacy warranting further clinical evaluation. Results from 24 more patients treated with Radspherin® in the RAD-18-002 study are pending. The Journal of Surgical Oncology publication is available online at: https://onlinelibrary.wiley.com/doi/full/10.1002/jso.27897 About the RAD-18-002 Study RAD-18-002 is a Phase 1/2a open-label study designed to select the clinical dose, and evaluate the safety, tolerability, and signal of efficacy of intraperitoneally administered Radspherin® in patients with peritoneal metastases from colorectal cancer scheduled for cytoreduction and HIPEC. The study was closed for recruitment at the end of 2023. About Radspherin® Radspherin® is an investigational radiopharmaceutical designed for the local treatment of cancer that has spread to body cavities. It consists of billions of calcium carbonate microparticles containing the radioactive material radium-224. The mode of action is the decay of radium-224 emitting alpha-particles, a highly potent form of ionizing radiation. Radspherin® is investigated in ongoing clinical studies to treat peritoneal metastases from ovarian and colorectal cancer and it is administered intraperitoneally after surgical resection with removal of all macroscopic tumors. About Oncoinvent Oncoinvent AS is a clinical stage, radiopharmaceutical company developing innovative treatments for solid cancers. The technology platform is focused on the use of alpha-emitting radionuclides to deliver powerful radiation directly to cancer cells. The Company’s lead product candidate, Radspherin ® , is being advanced through clinical development by a carefully composed team with experience from all stages of radiopharmaceutical development. Internal manufacturing and supply chain capabilities have been established, which now have the capacity to supply Radspherin ® for multi-center phase 2 clinical studies. For additional information, please visit www.oncoinvent.com . Forward-Looking Statements All statements other than statements of historical facts contained in this press release are forward-looking statements and are not a representation that Oncoinvent’s plans, estimates, or expectations will be achieved. These forward-looking statements represent Oncoinvent’s expectations as of the date of this press release, and Oncoinvent disclaims any obligation to update the forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to whether the results of clinical or other studies will support the use of our product offerings, the impact of results of such studies, our expectations of the reliability, accuracy and performance of our tests, or of the benefits of our tests and product offerings to patients, providers and payers.

- 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.