zevorcabtagene autoleucel (CT053) / CARsgen, Huadong Medicine - LARVOL DELTA

CARsgen Therapeutics Introduced Zhuhai SB Xinchuang to Accelerate Allogeneic CAR-T Cell Products Development in Mainland China (PRNewswire) - "CARsgen Therapeutics...announces reaching agreements with an investment fund managed by Zhuhai Hengqin SB Xinchuang Equity Investment Management Enterprise (Limited Partnership) ('Zhuhai SB Xinchuang') to jointly invest in UCARsgen Biotech Limited ('UCARsgen')....Under the agreements, UCARsgen has secured the exclusive rights in mainland China for the research, development, manufacture, and commercialization of the following allogeneic CAR-T products from CARsgen Therapeutics: the BCMA-targeted allogeneic CAR-T cell therapy for the treatment of multiple myeloma and plasma cell leukemia and the CD19/CD20 dual-targeted allogeneic CAR-T cell therapy for the treatment of B-cell malignancies."

Licensing / partnership • Hematological Malignancies • Multiple Myeloma

Long Term Follow-up Observational Study in Patients Treated with Gene-Modified T-Cell Therapy (clinicaltrials.gov) - P=N/A | N=1500 | Not yet recruiting | Sponsor: CARsgen Therapeutics Co., Ltd.

New trial • Hematological Malignancies • Multiple Myeloma • Oncology

Subgroup Analyses of Phase 2 Study: Evaluating the Efficacy of Fully Human BCMA-Targeting CAR T Cells (Zevorcabtagene Autoleucel) in Patients with Relapsed/Refractory Multiple Myeloma (ASH 2024) - P1/2 | "Zevorcabtagene autoleucel (zevor‑cel) is a fully human, BCMA-targeting autologous CAR T-cell therapy...There was a trend towards favorable outcomes which was seen in patients without high-risk cytogenetics compared to those with high-risk cytogenetics : 18m DOR rate of 66% versus 58%, 18m PFS rate of 69% versus 56% and an estimated 30m OS rate of 85% versus 76%, however, none of these differences were statistically significant. Conclusion The subgroup analyses of the pivotal Phase II stage of LUMMICAR STUDY 1 indicated that the clinical efficacy of zevor‑cel is not significantly impacted by baseline characteristics suggesting that even patients with RRMM with poor prognostic factors may benefit from zevor-cel."

CAR T-Cell Therapy • Clinical • P2 data • Hematological Malignancies • Multiple Myeloma • Oncology

Subgroup Analyses of Phase 2 Study: Evaluating the Efficacy of Fully Human BCMA-Targeting CAR T Cells (Zevorcabtagene Autoleucel) in Patients with Relapsed/Refractory Multiple Myeloma (PRNewswire) - P1/2 | N=121 | LUMMICAR STUDY 1 (NCT03975907) | Sponsor: CARsgen Therapeutics Co., Ltd. | "CARsgen Therapeutics Holdings Limited...announces that the Company will present the clinical data of zevorcabtagene autoleucel...at the 66th Annual Congress of the American Society of Hematology....In 102 patients with RRMM who had received at least 3 prior lines of therapy including an immunomodulatory drug and a proteasome inhibitor, the objective response rate (ORR) was 92.2%, the stringent complete response (sCR) or complete response (CR) was 71.6%. The ORR or the CR/sCR rate was not affected by any of the baseline characteristics tested. With a median follow-up of 20.3 (range: 0.4 to 27) months, the median duration of response (DOR), progression-free survival (PFS), and overall survival (OS) data were not mature and therefore, 18-month (18m) and estimated 30-month (30m) event free rates were used as efficacy outcomes for subgroup analyses."

P2 data • Multiple Myeloma

CARsgen U.S. Clinical Holds Lifted by FDA (PRNewswire) - "CARsgen Therapeutics Holdings Limited...announces that the U.S. Food and Drug Administration ('FDA') lifted the clinical holds on clinical trials of zevorcabtagene autoleucel (zevor-cel, CT053, an autologous CAR-T product against BCMA), satricabtagene autoleucel (satri-cel, CT041, an autologous CAR-T product against Claudin18.2), and CT071 (an autologous CAR-T product against GPRC5D) in the United States."

FDA event • Hematological Malignancies • Oncology

A Real-World Observational Study: Zevorcabtagene Autoleucel Injection in Patients with Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P=N/A | N=200 | Not yet recruiting | Sponsor: CARsgen Therapeutics Co., Ltd.

New trial • Real-world • Real-world evidence • Hematological Malignancies • Multiple Myeloma • Oncology

VOLUNTARY ANNOUNCEMENT TO PRESENT ZEVORCABTAGENE AUTOLEUCEL, CT071 AND CT0590 AT ASH 2024 ANNUAL CONGRESS (HKEXnews) - "The board of directors of the Company...announces that the Company will present the clinical data of zevorcabtagene autoleucel...CT071 (an autologous CAR T-cell therapy candidate targeting GPRC5D), and CT0590 (an allogeneic CAR T-cell product candidate against BCMA) at the 66th Annual Congress of the American Society of Hematology ('ASH'). Abstracts and further details will be announced after November 5, 2024 Eastern Time."

Clinical data • Hematological Malignancies • Leukemia • Multiple Myeloma • Oncology

CARsgen Submitted Application to Request Lifting Clinical Holds to FDA (CARsgen Press Release) - "CARsgen Therapeutics Holdings Limited...announces that the U.S. Food and Drug Administration ('FDA') recently did a follow-up inspection of the manufacturing site located in Durham, North Carolina. The inspection was positive, and no observation (Form 483) was issued. The Company has submitted the complete response letters to request lifting the clinical holds for zevorcabtagene autoleucel, satricabtagene autoleucel and CT071 to FDA on October 4, 2024. FDA is expected to respond within 30 calendar days."

FDA event • Oncology

CARsgen Announces 2024 Interim Results (PRNewswire) - "CARsgen has been collaborating with Huadong Medicine for the commercialization of zevor-cel in mainland China. As of July 31, 2024, zevor-cel had been included in nearly 20 provincial or municipal government-subsidized insurance programs and private health insurance products; certification and regulatory filings had been completed in over 100 healthcare institutions across 19 provinces or cities nationwide; we had received a total of 52 orders from Huadong Medicine...The Group's revenue was over RMB6 million for the six months ended June 30, 2024 mainly from zevor-cel in which the primary revenue of zevor-cel was calculated on the basis of ex-works price, rather than on the basis of end-of-market prices....Besides, the Company received a milestone payment of RMB75 million from Huadong Medicine for zevor-cel for the six months ended June 30, 2024....Data updates for CT071 and CT0590 are to be disclosed in the second half of 2024."

Clinical data • Commercial • Hematological Malignancies • Multiple Myeloma • Oncology

Keji Pharmaceutical-B (2171.HK): CARsgen plans to list CT041 and submit an NDA in the first half of 2025 [Google translation] (FUTU) - "CT041 is a potential global first-of-its-kind autologous CAR-T candidate targeting CLDN 18.2...it is planned to submit an NDA to the NMPA in the first half of 2025....With CT053 and CT041 approved for listing, we expect the company's revenue for 2024-2026 to be 100 million yuan, 300 million yuan, and 700 million yuan, respectively."

China filing • Commercial • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor

CARsgen Presents Phase II Results on Zevorcabtagene Autoleucel and First-in-human CT071 Results at EHA 2024 [Google translation] (CARsgen Press Release) - "CARsgen Therapeutics...announces that the updated results of zevorcabtagene autoleucel (zevor-cel; R&D code: CT053, an autologous CAR T-cell product targeting BCMA) and CT071 (an autologous CAR T-cell product targeting GPRC5D) have been presented at the 29th Annual Congress of the European Hematology Association...The results of LUMMICAR STUDY 1 of zevorcabtagene autoleucel were reported as an oral presentation at the 29th EHA Annual Congress on June 15, 2024, 17:30-17:45 CEST....The preliminary results of Phase I of CT071 were presented as a poster at the 29th EHA Annual Congress on June 14, 2024, 18:00 - 19:00 CEST..."

Clinical data • Hematological Malignancies • Multiple Myeloma • Oncology

The research results of Keji Pharmaceutical's Xikaize Phase II clinical trial and CT071 first-in-human trial were unveiled at the 2024 EHA [Google translation] (Pharm News) - P1/2 | N=121 | LUMMICAR STUDY 1 (NCT03975907) | Sponsor: CARsgen Therapeutics Co., Ltd. | "The results of the zevor-cel LUMMICAR STUDY 1 study were presented orally at the 29th EHA Annual Meeting on June 15, 2024, at 17:30-17:45 CEST...Right off the bat Early start-up operation of the phase II cohort (n=102) of the phase I/II study LUMMICAR-1 in R/R MM who had received at least 3 lines of previous treatment and with acceptable safety...92.2% of people interested in investigating the plan (ORR), 73 people in the group (71.6%) (sCR, n= 70) After completion (CR, n=3)....The PFS of all patients at 12 and 18 months was 76.3% (95% CI: 66.45, 83.56) 61.9% (95% CI: 51.19, 70.85) 90.2% of people (95% CI: 82.55, 94.60) and 79.4% (95% CI: 69.69, 86.29). 8.66) and 87.7% (95% CI: 76.56, 93.77)."

P2 data • Hematological Malignancies • Multiple Myeloma • Oncology

Zevorcabtagene Autoleucel: First Approval. (PubMed, Mol Diagn Ther) - "Clinical studies of zevorcabtagene autoleucel are underway in Canada and the US. This article summarizes the milestones in the development of zevorcabtagene autoleucel leading to this first approval for relapsed or refractory multiple myeloma."

Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology

PHASE 2 STUDY OF FULLY HUMAN BCMA-TARGETING CAR-T CELLS (ZEVORCABTAGENE AUTOLEUCEL) IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (EHA 2024) - P1/2 | "A single infusion of zevor-cel (target dose of 150× 106 or 180 × 106 CAR-positive T cells based on body weight of ≤80 kg or >80 kg, respectively) wasadministered 1 to 2 days after the completion of lymphodepletion (fludarabine 25 mg/m2 andcyclophosphamide 300 mg/ m2 daily for 3 consecutive days)... The longer follow-up data reaffirmed that zevor-cel induces deep and durable responses that mature over timein heavily pre-treated patients with RRMM with an encouraging safety profile."

CAR T-Cell Therapy • Clinical • P2 data • Bone Marrow Transplantation • Hematological Malignancies • Infectious Disease • Inflammation • Multiple Myeloma • Oncology • Pneumonia • Respiratory Diseases • Transplantation

Clinical Trial to Evaluate CT053 in Patients With Relapsed and/or Refractory Multiple Myeloma (LUMMICAR STUDY 1) (clinicaltrials.gov) - P1/2 | N=121 | Active, not recruiting | Sponsor: CARsgen Therapeutics Co., Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology

MATCHING-ADJUSTED INDIRECT COMPARISON OF EFFECTIVE CHARACTERISTICS AMONG DIFFERENT BCMA TARGETING CAR-T IN TREATMENT OF RELAPSED OR REFRACTORY MULTIPLE MYELOMAS (EBMT 2024) - P1/2, P1b, P2 | "This analysis used matching-adjusted indirect comparisons (MAIC) to evaluate the comparative efficacy of Equecabtagene Autoleucel (Eque-cel) versus Ciltacabtagene Autoleucel (Cilta-cel) , Idecabtagene vicleucel (ide-cel), zevorcabtagene autoleucel (zevor-cel, CT053) in patients with relapsed or refractory multiple myeloma. After matching and adjusting for clinically relevant prognostic factors, eque-cel demonstrated a better trend of short-term efficacy when compared to cilta-cel of CARTIFAN study, ide-cel of KARMMA study and zevor-cel of LUMMICAR study. Eque-cel also showed a favorable long-term efficacy in patients with heavily pretreated relapsed or refractory MM"

Hematological Malignancies • Multiple Myeloma • Oncology

MATCHING-ADJUSTED INDIRECT COMPARISON OF EFFECTIVE CHARACTERISTICS AMONG DIFFERENT BCMA TARGETING CAR-T IN TREATMENT OF RELAPSED OR REFRACTORY MULTIPLE MYELOMAS (EBMT 2024) - P1/2, P1b, P2 | "This analysis used matching-adjusted indirect comparisons (MAIC) to evaluate the comparative efficacy of Equecabtagene Autoleucel (Eque-cel) versus Ciltacabtagene Autoleucel (Cilta-cel) , Idecabtagene vicleucel (ide-cel), zevorcabtagene autoleucel (zevor-cel, CT053) in patients with relapsed or refractory multiple myeloma. After matching and adjusting for clinically relevant prognostic factors, eque-cel demonstrated a better trend of short-term efficacy when compared to cilta-cel of CARTIFAN study, ide-cel of KARMMA study and zevor-cel of LUMMICAR study. Eque-cel also showed a favorable long-term efficacy in patients with heavily pretreated relapsed or refractory MM"

Hematological Malignancies • Multiple Myeloma • Oncology

Clinical Trial to Evaluate CT053 in Patients With Relapsed and/or Refractory Multiple Myeloma (LUMMICAR STUDY 1) (clinicaltrials.gov) - P1/2 | N=120 | Recruiting | Sponsor: CARsgen Therapeutics Co., Ltd. | Trial primary completion date: Dec 2023 ➔ Dec 2024

Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

NMPA Approves the NDA for CARsgen's BCMA CAR-T Therapy Zevorcabtagene Autoleucel for Relapsed or Refractory Multiple Myeloma (PRNewswire) - "CARsgen Therapeutics Holdings Limited...announces that today the National Medical Products Administration ('NMPA') of China has approved the New Drug Application ('NDA') for zevorcabtagene autoleucel (R&D code: CT053, an autologous CAR-T product candidate against BCMA), for the treatment of adult patients with relapsed or refractory multiple myeloma who have previously progressed after at least 3 lines of therapy (including a proteasome inhibitor and immunomodulator agent)....The approval of zevorcabtagene autoleucel is based on an open-label, single arm, multi-center Phase II clinical trial (LUMMICAR STUDY 1, NCT03975907) conducted in China."

Non-US regulatory • Hematological Malignancies • Multiple Myeloma • Oncology

Clinical Trial to Evaluate Zevor-cel (CT053) in Patients With Relapsed and/or Refractory Multiple Myeloma (LUMMICAR STUDY 2) (clinicaltrials.gov) - P1/2 | N=105 | Active, not recruiting | Sponsor: CARsgen Therapeutics Co., Ltd. | Recruiting ➔ Active, not recruiting | Phase classification: P1b/2 ➔ P1/2

Enrollment closed • IO biomarker • Phase classification • Hematological Malignancies • Multiple Myeloma • Oncology

FDA Puts Clinical Hold on Three CARsgen Therapeutics CAR-T Candidates (BioSpace) - "The FDA has placed a clinical hold on three of CARsgen Therapeutics’ CAR-T cell therapy candidates following an inspection of the Chinese biotech’s manufacturing facility in Durham, North Carolina...CARsgen notified the Hong Kong Stock Exchange that the FDA clinical hold had gone into effect on three of its CAR-T products: CT053, CT071 and CT041. According to CARsgen, the clinical hold on its products are due to chemistry, manufacturing, and controls-related 'questions' that arose due to the FDA inspection....The company said in the notice that it plans to conduct a 'comprehensive review' and improve its Current Good Manufacturing Practices (cGMP) at the facility, which was opened in February 2022."

FDA event • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Pancreatic Cancer • Solid Tumor

Three-Year Follow-up on Efficacy and Safety Results from Phase 1 Lummicar Study 1 of Zevorcabtagene Autoleucel in Chinese Patients with Relapsed or Refractory Multiple Myeloma (ASH 2023) - P1/2 | "Introduction: Phase 1b of LUMMICAR STUDY 1 was conducted in China (NCT03975907) for zevorcabtagene autoleucel (zevor-cel, CT053), a fully human autologous chimeric antigen receptor (CAR) T-cell therapy comprising a B-cell maturation antigen-specific single-chain variable fragment, in patients with relapsed or refractory multiple myeloma (RRMM)... At approximately 3 years of follow-up, heavily pre-treated RRMM patients maintained deep and durable responses after receiving a single infusion of zevor-cel, which showed a well-managed safety profile in the ongoing long-term follow-up."

Clinical • P1 data • Hematological Disorders • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology

CARsgen Presents Updated Research Results on Zevor-cel at 2023 ASH Annual Meeting (PRNewswire) - P1 | N=114 | LUMMICAR-1 (NCT03975907) | Sponsor: CARsgen Therapeutics Co., Ltd. | "CARsgen Therapeutics Holdings Limited...announces that at the 2023 American Society of Hematology ('ASH') Annual Meeting, the Company presented one poster with study results for zevorcabtagene autoleucel ('zevor-cel', R&D code: CT053, an autologous CAR T-cell therapy candidate against BCMA), which include the 3-year follow-up on efficacy and safety results from the Phase I portion of Phase I/II registrational study in China (LUMMICAR-1, NCT03975907)....The overall response rate (ORR) was 100% (14/14) with 78.6% (11/14) patients achieving a complete response (CR) or a stringent complete response (sCR); minimal residual disease (MRD) negativity was attained in all patients achieving either a CR or sCR. The median duration of response (mDOR) was 24.1 months in all patients and 26.0 months in those achieving CR or sCR."

P1 data • Hematological Malignancies • Multiple Myeloma • Oncology

CARsgen Announced 2023 Interim Results (PRNewswire) - "Zevor-cel is expected to be approved by the NMPA for the treatment of R/R MM at the end of 2023 or the beginning of 2024."

Non-US regulatory • Hematological Malignancies • Multiple Myeloma • Oncology

CARsgen Announced 2022 Annual Results and Business Updates (PRNewswire) - "Zevor-cel is an upgraded fully human, autologous BCMA CAR T-cell product candidate for the treatment of R/R MM....CARsgen plans to submit a Biologics License Application (BLA) to the U.S. FDA in 2024....For CT041, the first-in-class CAR T-cell product candidate against CLDN18.2, a confirmatory Phase II clinical trial for advanced GC/GEJ in China is ongoing. A Phase 2 clinical trial in the U.S. is expected to initiate in the first half of 2023....CARsgen plans to submit an NDA to the NMPA in China in the first half of 2024 and plans to submit the BLA to the U.S. FDA in 2025."

BLA • New P2 trial • Non-US regulatory • Trial status • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor