A Multicenter, Single-arm, Phase 2 Study to Evaluate the Efficacy, Safety and Pharmacokinetics of RC88 Monotherapy in Platinum-resistant Recurrent Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer

The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of RC88 monotherapy in subjects with Platinum-Resistant Recurrent Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer.

Start Date19 Jan 2024

Sponsor / Collaborator

RemeGen Co., Ltd.

CTR20233195 / RecruitingPhase 2

一项评价RC88在铂耐药复发上皮性卵巢癌、输卵管癌和原发腹膜癌中的有效性、安全性和药代动力学的多中心、单臂II期临床研究

[Translation] A multicenter, single-arm phase II clinical study to evaluate the efficacy, safety, and pharmacokinetics of RC88 in platinum-resistant recurrent epithelial ovarian cancer, fallopian tube cancer, and primary peritoneal cancer

主要研究目的：评价RC88单药治疗铂耐药复发上皮性卵巢癌/输卵管癌/原发腹膜癌的有效性。次要研究目的：评价RC88单药治疗铂耐药复发上皮性卵巢癌/输卵管癌/原发腹膜癌中的安全性、药代动力学特征和免疫原性。

[Translation]

The primary study objective is to evaluate the efficacy of RC88 monotherapy in the treatment of platinum-resistant recurrent epithelial ovarian cancer/fallopian tube cancer/primary peritoneal cancer. The secondary study objective is to evaluate the safety, pharmacokinetic characteristics and immunogenicity of RC88 monotherapy in the treatment of platinum-resistant recurrent epithelial ovarian cancer/fallopian tube cancer/primary peritoneal cancer.

Start Date11 Jan 2024

Sponsor / Collaborator

RemeGen Co., Ltd.

CTR20232413 / RecruitingPhase 1/2

评价RC148注射液单药及联合方案治疗局部晚期不可切除或转移性恶性实体肿瘤患者的疗效和安全性的多中心Ⅰ/Ⅱ期临床研究

[Translation] A multicenter phase I/II clinical study to evaluate the efficacy and safety of RC148 injection alone and in combination with other drugs in the treatment of patients with locally advanced unresectable or metastatic malignant solid tumors

本研究为多中心、开放性I/II 期临床研究。I期旨在评估单药的安全性、耐受性、最大耐受剂量（MTD）/最大给药剂量（MAD）、II期临床试验的推荐剂量（RP2D）、药代动力学（PK）、药效动力学（PD）、免疫原性、以及初步的抗肿瘤疗效；Ⅱ期探索RC148 联合多西他赛/维迪西妥单抗（RC48）/RC88 在晚期恶性实体瘤的有效性、安全性、耐受性、PK和免疫原性。

[Translation]

This study is a multicenter, open-label Phase I/II clinical study. Phase I aims to evaluate the safety, tolerability, maximum tolerated dose (MTD)/maximum administered dose (MAD), recommended dose for Phase II clinical trial (RP2D), pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and preliminary anti-tumor efficacy of a single drug; Phase II explores the efficacy, safety, tolerability, PK, and immunogenicity of RC148 combined with docetaxel/vedicizumab (RC48)/RC88 in advanced malignant solid tumors.

Start Date07 Sep 2023

Sponsor / Collaborator

RemeGen Co., Ltd.

100 Clinical Results associated with Misitatug blivedotin

100 Translational Medicine associated with Misitatug blivedotin

100 Patents (Medical) associated with Misitatug blivedotin

Literatures (Medical) associated with Misitatug blivedotin

01 Jul 2023·Clinical and translational science

Translation of the efficacy of antibody-drug conjugates from preclinical to clinical using a semimechanistic PK/PD model: A case study with RC88.

Article

Author: Ma, Xinting ; Zhao, Guorui ; Liu, Zhihao ; Zhang, Jinfeng ; Jiang, Jing ; Li, Qiaoning ; Wang, Ling

Three semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) models, Simeoni, Jumbe, and Hybrid, were used for the efficacy translation of RC88 from preclinical to clinical. RC88 is a mesothelin-targeting antibody-drug conjugate for malignant solid tumor. In the preclinical study, the relationship between PKs and PDs was determined using the xenograft mouse model derived from ovarian cancer and lung cancer cell lines. A secondary parameter representing the efficacy index of the drug, termed as tumor static concentration (TSC), was calculated using the three semimechanistic PK/PD models. A mechanism-based target-mediated drug disposition model was used to predict the human PKs. TSC from mice and predicted human PK were integrated to predict human efficacy dose. Results showed that 2 cell lines were sensitive to drugs, and the predicted efficacy dose was between 0.82 and 1.96 mg/kg q1w.

02 Jan 2023·Drug and chemical toxicologyQ4 · MEDICINE

Preclinical safety profile of RC88-ADC：a novel mesothelin-targeted antibody conjugated with Monomethyl auristatin E

Q4 · MEDICINE

Article

Author: Li, Shoufeng ; Li, Shenjun ; Jiang, Jing ; Tang, Naping ; Xin, Wei ; Wang, Ling

Mesothelin (MSLN) is an attractive therapeutic target for antibody drug conjugates (ADC) because of significant differences in expression pattern between diseased and normal tissues. RC88-ADC is a novel ADC, targeting MSLN, and inhibits tumor growth significantly in mice xenograft models. We performed an 11-week repeated dose toxicity study of RC88-ADC via intravenous injection in Cynomolgus Monkeys with an 8-Week recovery period according to International Conference on Harmonization (ICH) S9 and S6(R1). RC88-ADC was administered to groups of 5 male and 5 female monkeys at dose levels of 2.5, 5, and 10 mg/kg/2 weeks, meanwhile vehicle, naked antibody, small molecule groups were set up as the control. 4 animals died in 10 mg/kg group of RC88-ADC. The clinical symptoms mainly included ocular toxicity, weight loss and food intake decrease in the middle and high dose groups of RC88-ADC. RC88-ADC caused dose-related reversible myelosuppression, manifested as hematologic toxicity, which was consistent with the small molecule toxicity profile of its coupling. The highest non-severely toxic dose of RC88-ADC was 5 mg/kg in monkeys after repeated dosing. Nonetheless, the integrated analysis showed that RC88-ADC demonstrated an acceptable safety profile and provided an improved treatment window. These results pave the way for further investigation of RC88-ADC in humans.

News (Medical) associated with Misitatug blivedotin

05 Jun 2024

·www.prnewswire.com

RemeGen Showcases Research Results at American Society of Clinical Oncology (ASCO) 2024 Annual Meeting, Highlighting Its Prolific Innovation in Global Cancer Treatment

YANTAI, China, June 5, 2024 /PRNewswire/ -- RemeGen Co., Ltd. ("RemeGen" or "the Company") (9995.HK, SHA: 688331), a commercial-stage biotechnology company, showcased its innovation in the field of global cancer treatment at the American Society of Clinical Oncology Annual Meeting (ASCO 2024) held in Chicago from May 31-June 4, 2024, sharing major research results including its proprietary antibody drug conjugates (ADCs) Disitamab Vedotin (RC48) and RC88. RemeGen's innovative drugs featured in one Clinical Science Symposium, five Poster presentations, and ten online Abstracts at ASCO 2024, covering multiple cancer types including gastric and bladder cancer, and gynecological tumors in studies that included both monotherapy and combination therapies. Dr. Jianmin Fang, CEO of RemeGen, commented, "It is always such an honor to present our latest research findings on an internationally renowned stage such as ASCO Annual Meeting 2024. This not only demonstrates RemeGen's leading position in the field of antibody-drug conjugates in China but also proves our commitment to continuing our research efforts to provide effective treatment options for patients worldwide." Clinical Science Symposium First author Professor Song Li from Qilu Hospital of Shandong University gave an oral presentation at a Clinical Science Symposium at ASCO 2024 based on a randomized, controlled (RCT) multicenter, single-arm, Phase II trial investigating the efficacy of RemeGen's disitamab vedotin (RC48) combined with toripalimab and the oral fluoropyrimidine S-1 in first-line HER2-overexpressing advanced gastric or gastroesophageal junction adenocarcinoma. Poster Sessions First author Professor Sheng Xinan from Peking University Cancer Hospital presented RemeGen's poster session (Poster #263) of a Phase II study of neoadjuvant treatment with disitamab vedotin plus toripalimab in patients with HER2-expressing muscle-invasive bladder cancer (MIBC) focusing on the preliminary efficacy and safety results of RC48-C017. The standard of care for MIBC is neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy plus pelvic lymph node dissection (RC + PLND). Disitamab vedotin monotherapy, or combined therapy with toripalimab, showed promising anti-tumor activity in metastatic urothelial carcinoma. This Phase II trial aimed to evaluate the safety and efficacy of disitamab vedotin plus toripalimab as perioperative therapy in MIBC patients and the interim results presented at ASCO showed promising efficacy results with a manageable safety profile in operable MIBC patients. These results support further investigation for disitamab vedotin plus toripalimab in this population. Other poster presentations included a Phase II multi-center study in poster session (poster #311a) on adjuvant or rescue disitamab vedotin (RC48-ADC) for high-risk non-muscle invasive bladder cancer with HER2 expression; and a prospective, single-arm, single-center clinical study in poster session (poster #513a) on disitamab vedotin combined with toripalimab in patients with advanced penile cancer who have progressed on treatment or are intolerant to cisplatin chemotherapy. Online Abstract Publications Ten other online abstracts accepted by ASCO reflected results of RemeGen's RC48 and RC88 in bladder, breast, and GI cancers, demonstrating the Company's prolific innovation in global cancer treatment. About ASCO The ASCO 2024 meeting is the premier event for strategies to improve quality care in oncology. It provides superb panels featuring experts who are leading and implementing innovative programs focused on value. ASCO's diverse network of nearly 42,350 oncology professionals recognizes ASCO's dedication to providing the highest-quality resources in education, policy, the pioneering of clinical research, and above all, advancing the care for patients with cancer. About RemeGen Co. Ltd. Founded in 2008, RemeGen (9995.HK, SHA: 688331) is a leading biopharmaceutical company in China committed to providing solutions to the unmet clinical needs of patients suffering from life-threatening illnesses. RemeGen has research laboratories and offices throughout China and the United States. The company is committed to discovering, developing, and commercializing innovative and differentiated biologic drugs of significant clinical value in the key therapeutic areas of autoimmune, oncology, and ophthalmic diseases. For more details, please visit: About Disitamab Vedotin (RC48) Disitamab Vedotin (RC48) is an investigational anti-HER2 antibody-drug conjugate targeting prevalent solid cancers with significant unmet medical needs and is the first domestically developed ADC to receive marketing approval in China. The company is implementing a differentiated development and commercial strategy for disitamab vedotin, including (i) gastric cancer (GC), (ii) urothelial carcinoma (UC), (iii) breast cancer (BC), and (iv) other HER2-expressing cancers. SOURCE RemeGen Co., Ltd

Clinical ResultASCOADCPhase 2

04 Jun 2024

·www.prnewswire.com

RemeGen Reports Proof-of-Concept Phase I/II Clinical Study Results for Self-Developed, Potential First-in-Class Antibody-Drug Conjugate RC88

YANTAI, China, June 3, 2024 /PRNewswire/ -- RemeGen Co., Ltd. ("RemeGen" or "the Company") (9995.HK, SHA: 688331), a commercial-stage biotechnology company, presented the results of the first-in-human, single-arm, open-label, multi-center Phase I/II study evaluating RC88 in patients with MSLN-expressing advanced solid tumors on June 3, at the American Society of Clinical Oncology Annual Meeting (ASCO 2024) held in Chicago from May 31-June 4, 2024. The first author, Professor Liu Yutao, from the Chinese Academy of Medical Sciences Cancer Hospital, presented RemeGen's poster session (Poster #422) of this study that focused on efficacy and safety in patients with ovarian cancer, non-squamous non-small cell lung cancer, and cervical cancer. RC88 is a novel, first-in-class, antibody-drug conjugate (ADC) developed by RemeGen that targets mesothelin (MSLN) with a monomethyl auristatin E (MMAE) payload. MSLN, a glycosylphosphatidylinositol-anchored protein, is overexpressed in several solid tumors with limited expression in normal tissues. RC88 consists of a recombinant humanized anti-MSLN monoclonal antibody linked to MMAE which acts as a microtubule inhibitor. RC88 has a high affinity for MSLN and can specifically bind to MSLN overexpressing tissues. In this study, RC88 has demonstrated a terminating effect on tumor cells with various levels of MSLN expression. RC88 has demonstrated anti-tumor activity and a manageable RC88 monotherapy safety profile in MSLN-positive advanced solid tumors. Preclinical studies showed that RC88 can selectively deliver a potent cytotoxic payload to MSLN-expressing cells through internalization, thus inducing G2/M arrest and apoptosis. Patients with MSLN-expressing advanced malignant solid tumors that had failed standard therapies were enrolled in this study. For the Phase II study, the primary endpoint was overall response rate (ORR) per RECIST v1.1 criteria-based endpoints, with secondary endpoints including disease control rate (DCR), progression-free survival (PFS), and safety. As of February 21, 2024, 170 patients with advanced solid tumor were enrolled. The dose escalation phase was completed, and 2.0 mg/kg and 2.5 mg/kg Q3W doses were expanded into Phase II. In the ovarian cancer (OC) cohort, 54 patients were enrolled, all with 2+ or 3+ MSLN expression. Of these, 40 (74.1%) had an ECOG score of 1; 33 (61.1%) had received prior bevacizumab treatment, and 28 (51.9%) had prior PARP inhibitor (PARPi) exposure. As of March 22, 2024, a total of 31 patients in the 2.0mg/kg group who had received two to four lines of prior therapies were efficacy-evaluable. Among them, the ORR and confirmed ORR (cORR) were 45.2% (14/31, 95%CI 27.3, 64.0) and 41.9% (13/31, 95%CI 24.5, 60.9), respectively. The median DoR was 8.02 months (95%CI 2.83, 8.54). In the non-squamous non-small cell lung cancer (NSCLC) cohort, 16 EGFR/ALK wild-type (WT) patients were efficacy-evaluable. The ORR and cORR were 31.3% (5/16) and 25% (4/16), respectively. Among the above patients with MSLN high expression (PS2#≥50), the ORR, cORR, median PFS and median DoR were 41.7% (5/12), 33.3% (4/12), 6.87 months and 9.13 months, respectively. In the cervical cancer (CC) cohort, 18 patients who had progressed on previous systemic therapies were enrolled. The ORR and cORR were 33.3% (6/18) and 27.8% (5/18), respectively. Among the 12 patients that received ≥ 2 lines of therapies, the ORR and cORR were 41.7% (5/12) and 33.3% (4/12), respectively. "Currently, chemotherapy is the standard of care for OC with an ORR rate of 12%. The promising results of 41.9% ORR from this study underscore the potential of RC88 to significantly improve outcomes for patients with MSLN-expressing advanced solid tumors," said Dr. Fang Jianmin, CEO of RemeGen. "We are committed to advancing our innovative therapies to address these huge unmet medical needs and enhance patient care." About RemeGen Co. Ltd. Founded in 2008, RemeGen (9995.HK, SHA: 688331) is a leading biopharmaceutical company in China committed to providing solutions to the unmet clinical needs of patients suffering from life-threatening illnesses. RemeGen has research laboratories and offices throughout China and the United States. The company is committed to discovering, developing, and commercializing innovative and differentiated biologic drugs of significant clinical value in the key therapeutic areas of autoimmune, oncology, and ophthalmic diseases. For more details, please visit: About RC88 Independently developed by RemeGen, RC88 is a novel antibody drug conjugate (ADC) targeting mesothelin (MSLN). It uses the company's innovative bridging technology to connect antibodies and payloads. By design, RC88 molecule can mediate the endocytosis of antibodies by binding to MSLN-positive tumor cells, thereby effectively delivering cytotoxins to cancer cells and achieving improved tumor killing effects. SOURCE RemeGen Co., Ltd

Clinical ResultASCOADCPhase 2Phase 1

02 Feb 2024

·www.prnewswire.com

World Cancer Day 2024: RemeGen Announces Three Significant Developments in the Global Fight Against Cancer, Narrowing the Care Gap

YANTAI, China, Feb. 2, 2024 /PRNewswire/ -- RemeGen Co. Ltd.("RemeGen" or "the Company") (9995.HK, 688331.SH), a commercial-stage biotechnology company, with a mission that is closely aligned with the Close the Care Gap theme of World Cancer Day 2024 which falls on February 4, has announced three major developments that will further the global fight against cancer and forge new paths in tumor treatments. The Company not only endeavors to contribute to the field of anti-cancer treatments, but also provide much-improved medical opportunities and increased hope to all patients. Dr. Jianmin Fang, CEO of RemeGen, commented, "Cancer is the common enemy of mankind, and at RemeGen we feel a strong sense of responsibility and mission to continue to provide more effective and safer treatment options for cancer patients around the world through our cutting-edge innovation and research. On World Cancer Day 2024, we are proud to announce more advances in cancer drug research through drug discovery and collaboration with our partners. We are celebrating the progress of scientific research and working for a more just and healthier future. Our time is now, and our mission is clear. Let's act together for a world without cancers." RemeGen's three major recent developments On January 12, RemeGen announced that it enrolled its first patient on a Phase II study of Disitamab Vedotin combined with Zimberelimab to treat cervical cancer patients who have failed at least one first-line platinum-containing standard treatment. Preliminary data show that Disitamab Vedotin can significantly improve treatment efficiency and its safety is controllable. Zimberelimab, compared with the data of PD-1/PD-L1 single drugs approved for this indication (not head-to-head), displayed excellent long-term efficacy with a higher objective response rate (ORR) of 27.8%, a median progression-free survival (mPFS) of 3.7 months, a median overall survival (mOS) of 16.8 months, and a 2-year duration of response (DoR) rate of 55%. This study is a new combination treatment strategy that is expected to provide better options for cervical cancer patients and bring new hope. On January 15, RemeGen announced its RC88 combined with Sintilimab injection to treat advanced malignant entities in cooperation with Innovent Biologics was approved by the State Food and Drug Administration's for Center for Drug Evaluation (CDE). The Phase I/IIa clinical study in tumor patients approved by the CDE is an open, multi-center Phase I/IIa clinical study in patients with advanced malignant solid tumors expressing mesothelin (MSLN). It includes, but is not limited to, pleural mesothelioma, peritoneal mesothelioma, ovarian cancer, pancreatic cancer, and lung adenocarcinoma, gastric adenocarcinoma, triple-negative breast cancer, among other cancer types that may benefit to evaluate the efficacy, safety, tolerability, PK characteristics, immunogenicity, and preliminary results of RC88 combined with Sintilimab injection administered every three weeks. Also recently, a national multi-center clinical study of RemeGen's Disitamab Vedotin (RC48) combined with monoclonal antibody, Toripalimab, in the treatment of HER2-expressing advanced gastric cancer and other solid tumors, led by Professor Shen Lin from Peking University Cancer Hospital, was published in The Lancet sub-journal eClinicalMedicine. This study is the first to explore the safety and efficacy of antibody drug conjugates (ADC) combined with immunotherapy in patients with HER2-positive and HER2-low-expressing gastric cancer. The study results show that Disitamab Vedotin combined with Toripalimab has a controllable safety profile and is effective in patients with HER2-positive and HER2-low-expressing gastric cancer or gastroesophageal junction (G/GEJ) cancer, displaying encouraging efficacy. About World Cancer Day World Cancer Day is a leading international awareness day held every February 4 and is the global uniting initiative led by the Union for International Cancer Control (UICC). By raising worldwide awareness, improving education and catalyzing personal, collective and government action, organizers all work together to reimagine a world where millions of preventable cancer deaths are saved and access to life-saving cancer treatment and care is equitable for all - no matter who you are or where you live. About RemeGen Co. Ltd. Founded in 2008, RemeGen (9995.HK, SHA: 688331) is a leading biopharmaceutical company in China committed to providing solutions to the unmet clinical needs of patients suffering from life-threatening illnesses. RemeGen has research laboratories and offices throughout China and the United States. The company is committed to discovering, developing, and commercializing innovative and differentiated biologic drugs of significant clinical value in the key therapeutic areas of autoimmune, oncology, and ophthalmic diseases. For more details, please visit: SOURCE RemeGen Co., Ltd

Phase 2Clinical ResultImmunotherapyDrug Approval

100 Deals associated with Misitatug blivedotin

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Indication	Highest Phase	Country/Location	Organization	Date
Recurrent Platinum-Resistant Primary Peritoneal Carcinoma	Phase 2	CN	RemeGen Co., Ltd.	19 Jan 2024
Platinum-Resistant Epithelial Ovarian Carcinoma	Phase 2	CN	RemeGen Co., Ltd.	11 Jan 2024
Platinum-Resistant Fallopian Tube Carcinoma	Phase 2	CN	RemeGen Co., Ltd.	11 Jan 2024
Advanced Malignant Solid Neoplasm	Phase 2	CN	RemeGen Co., Ltd.	14 Apr 2020
Mesothelioma	Phase 2	CN	RemeGen Co., Ltd.	14 Apr 2020
Adenocarcinoma of Lung	Phase 1	CN	RemeGen Co., Ltd.	23 Jun 2022
Bile Duct Neoplasms	Phase 1	CN	RemeGen Co., Ltd.	23 Jun 2022
Pancreatic Cancer	Phase 1	CN	RemeGen Co., Ltd.	-
Recurrent Platinum-Resistant Fallopian Tube Carcinoma	IND Approval	CN	RemeGen Co., Ltd.	26 Aug 2024
Malignant Mesothelioma of Peritoneum	IND Approval	CN	RemeGen Co., Ltd.	12 Jan 2024

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


PRNewswire Manual	Phase 1/2	Ovarian Cancer \| Uterine Cervical Cancer \| Non-squamous non-small cell lung cancer MSLN	170	RC88 2.0 mg/kg (OC)	ruenhkrrvi(keqvhreysf) = xigbpipjrq cexgghkttg (yrhncujize, 27.3 - 64.0) View more	Positive	03 Jun 2024
				RC88 (NSCLC)	ruenhkrrvi(keqvhreysf) = stacdhpfwn cexgghkttg (yrhncujize ) View more
NCT04175847 (RC88-C001, ASCO2024) Manual	Phase 1/2	Ovarian Cancer \| Uterine Cervical Cancer \| Non-squamous non-small cell lung cancer MSLN Expression	164	RC88 2.0 mg/kg	(xpithaquit) = rknbutpqod yomcogsrsf (pxhcufbnwj ) View more	Positive	24 May 2024
				RC88 2.5 mg/kg	(xpithaquit) = cbvntniqgz yomcogsrsf (pxhcufbnwj ) View more

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