Multiple CAR-T Therapies Achieve Over 90% Response Rates; Cell Therapy Keeps 100% of Patients Relapse-Free for Nearly 20 Months | CGT Weekly Report

Dec 15, 2024 07:30 CST Updated 07:30

Johnson & Johnson

Medical Device R&D and Manufacturer

▎Edited by the WuXi AppTec content team

Recently, the global cell and gene therapy (CGT) field has seen a series of advancements. Multiple chimeric antigen receptor (CAR) T-cell therapies have shown outstanding performance in early clinical studies, with an overall response rate (ORR)/objective response rate exceeding 90%.NRTX-1001, a regenerative cell candidate therapy derived from human pluripotent stem cells, for the treatment of drug-resistant mesial temporal lobe epilepsy (MTLE)Patients: The first two patients receiving low-dose treatment reported a reduction in seizures of >97% two years after a single treatment.Off-the-shelf γδ T cell therapy INB-100 for elderly patients with hematologic malignancies undergoing haploidentical hematopoietic stem cell transplantation (HSCT) after reduced-intensity conditioning (RIC) achieved 100% success in a Phase 1 clinical trial.Acute Myeloid Leukemia (AML)At a median follow-up time of 19.7 months, the patients remained in complete remission (CR), including three AML patients with high-risk cytogenetic features.This article will provide a brief introduction to some of the important advances excerpted for readers' reference only.

Image Source: 123RF

———✦Research and Development Progress✦———

◇ Johnson & Johnson announced the Phase 3 clinical trial CARTITUDE-4Latest Research ResultsThe results showed that, in patients with relapsed or refractory multiple myeloma (RRMM) who had received 1 to 3 prior treatment regimens (including proteasome inhibitors) and were lenalidomide-resistant, a single infusion of the B-cell maturation antigen (BCMA)-targeted CAR-T cell therapy Carvykti (cilta-cel), co-developed with Legend Biotech, significantly improved the minimal residual disease (MRD) negativity rate compared to standard treatment regimens.At a median follow-up of 34 months, the MRD negativity rate in evaluable patients was more than double in the cilta-cel treatment group compared to the standard treatment group (89% vs. 38%; p<0.0001). At 30 months post-treatment, the proportion of evaluable patients in the cilta-cel group who sustained (for 12 months or longer) MRD-negative complete response or better was five times that of the standard treatment group (52% vs. 10%; p<0.0001).

◇ Protara Therapeutics Announces Open-Label Phase 2 Clinical Trial ADVANCED-2Latest Results. This trial evaluated its basis on an inactivated Streptococcus pyogenes (Streptococcus pyogenes) The efficacy of the investigational cell therapy TARA-002 in patients with non-muscle invasive bladder cancer (NMIBC) carrying high-risk carcinoma in situ, including those who are unresponsive to or are initially treated with Bacillus Calmette-Guérin (BCG). The results showed,In all patients, the CR rate at 6 months after treatment was 72% (13/18), and the CR rate at any time point was 70% (14/20).Among the 3 evaluable patients with a follow-up time of 9 months, 2 remained in CR at 9 months. Additionally,In the cohort of patients non-responsive to BCG, the CR rate at 6 months of treatment was 100% (4/4), and the CR rate at any time point was 80% (4/5).

◇ Beacon Therapeutics announced the 3-month results from the Phase 2 clinical trial, DAWN, evaluating the investigational gene therapy laru-zova (AGTC-501) for the treatment of patients with X-linked retinitis pigmentosa (XLRP).Mid-term Data。Data show early signs of improvement in low-luminance visual acuity (LLVA), a key measure of visual function, in patients treated with laru-zova for 3 months.Laru-zova is a gene therapy based on adeno-associated virus (AAV) vector that expresses the full-length RPGR protein, thus has the potential to address all photoreceptor damage caused by XLRP, including the loss of rod and cone cells, representing a potential "best-in-class" treatment option for progressive vision loss in patients with XLRP.

◇ Arcellx Announces Positive Data from Pivotal Phase 2 Study iMMagine-1 of Its BCMA-Targeted CAR-T Cell Therapy Anitocabtagene Autoleucel (Anito-cel) for the Treatment of RRMM. Data as of October 31, 2024.The median follow-up time was 9.5 months, with an ORR of 97% (83/86) in 86 evaluable patients, a CR/strict CR (sCR) rate of 62% (53/86), and a very good partial response or better (≥VGPR) rate of 81% (70/86).The progression-free survival rate and overall survival rate at 6 months were 93.3% and 96.5%, respectively, while the progression-free survival rate and overall survival rate at 12 months were 78.5% and 96.5%, respectively.In the previous phase 1 study, at a median follow-up time of 38.1 months, the median progression-free survival for RRMM patients was 30.2 months.To date, no late-onset neurotoxicity caused by anito-cel has been observed in more than 150 patients dosed in the previous phase 1 study and the iMMagine-1 study.

◇ Poseida Therapeutics announced interim data from the Phase 1 trial of its BCMA-targeted allogeneic CAR-T therapy, P-BCMA-ALLO1, for the treatment of patients with RRMM. The results showed,The ORR was 91% in the optimized lymphodepletion group (Group C), 100% in patients who had not previously received BCMA-targeted therapy, and 86% in patients who had previously received at least one BCMA and/or GPRC5D-targeted therapy.In addition, the study also achieved significant safety outcomes, with no dose-limiting toxicity (DLT), low incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) (both ≤ grade 2), and no graft-versus-host disease (GVHD) or Parkinson's disease.

◇ Lyell Immunopharma announced preliminary data from the multicenter Phase 1/2 study of its CD19/CD20 dual-targeting autologous CAR-T cell therapy IMPT-314 for the treatment of patients with large B-cell lymphoma. Data as of October 22, 2024.The objective response rate was 94% and the CR rate was 72% among 17 evaluable patients.These patients had previously received at least two lines of treatment but had not been treated with CAR-T cell therapy. The safety of IMPT-314 is controllable, with no high-grade CRS and a low incidence of grade 3 ICANS. These adverse events can be resolved through standard treatment protocols.

◇ Synthekine announced preliminary results from the Phase 1 study of its CD19-targeted autologous CAR-T cell therapy, SYNCAR-001, in combination with the engineered pegylated IL-2 cytokine STK-009 for the treatment of relapsed or refractory CD19-positive hematologic malignancies. As of the data cutoff on October 8, 2024, the combination therapy demonstrated a favorable safety profile, with no DLT or IL-2-related toxicity observed, and no CRS > Grade 2 or ICANS > Grade 1.All (100%) non-Hodgkin lymphoma (NHL) patients treated with this combination therapy achieved CR and maintained CR at the data cutoff, with the longest CR duration exceeding 480 days.

◇ Neurona Therapeutics announced the results of its Phase 1/2 clinical trial for NRTX-1001, a regenerative cell therapy candidate derived from human pluripotent stem cells, for the treatment of drug-resistant mesial temporal lobe epilepsy. The results showed,The median number of disabling seizures in the low-dose group decreased by 92% from baseline, and 80% of patients reported a >75% reduction in seizures during the primary efficacy assessment period 7-12 months after starting treatment.The first two patients who received low-dose cell therapy still reported a reduction in seizures of >97% two years after a single treatment.Patients in the high-dose group experienced a 78% reduction in median disabling seizure frequency from baseline, with 60% reporting a >75% reduction in seizures during the interim assessment period of 4-6 months post-treatment. In both dose groups, no clinically significant cognitive or quality-of-life impairments were observed, and some participants showed significant improvement in test scores. Additionally, to date, both high-dose and low-dose NRTX-1001 have been well-tolerated.

◇ AAVantgarde Bio announced safety data for the first two subjects in the Phase 1/2 open-label clinical trial, LUCE-1. The study aims to evaluate the safety and tolerability of AAVB-081, an intraretinal gene therapy using AAV8 as a vector, for patients with retinitis pigmentosa associated with Usher syndrome type 1B (USH1B). AAVB-081 usesTwo AAV8 vectors, each carrying half of the target gene's information, recombine into a complete gene within the nucleus, thereby enablingGenerate therapeutic levels ofMYO7A protein. The results announced this time show,The best-corrected visual acuity (BCVA) of two subjects receiving low-dose treatment returned to pre-treatment levels within 2 weeks.All adverse events were mild and resolved without the need for further intervention. To date, no DLT has been observed.

◇ CRISPR Therapeutics announced the Phase 1/2 clinical trial data for its next-generation CD19-targeted allogeneic CAR-T cell therapy, CTX112, in treating relapsed or refractory CD19-positive B-cell malignancies. The results showed that CTX112 was well-tolerated at all dose levels and induced responses across all dose levels.Five of the 12 patients who received treatment had a duration of response lasting more than six months. One patient receiving Dose 1 remained in CR for one year after the initial infusion.

▲Clinical efficacy results of CTX112 (Image source: Reference [12])

◇ IN8bio announced updated data from the Phase 1 trial of its investigational off-the-shelf γδ T-cell therapy, INB-100, for elderly patients with hematologic malignancies undergoing haploidentical hematopoietic stem cell transplantation (HSCT) after reduced-intensity conditioning. Historical data indicates that approximately 25% of AML patients receiving HSCT are expected to relapse within 100 days post-transplant, with up to 50% experiencing relapse within one year. The results disclosed show,At a median follow-up time of 19.7 months, all (100%) AML patients treated with INB-100 remained in CR status, including three AML patients with high-risk cytogenetic features who, without maintenance therapy, still sustained CR for over three years.

———✦Financing, Cooperation, M&A✦———

Image Source: 123RF

◇ Chroma Medicine and Nvelop Therapeutics Announce MergerCombine epigenetic editing technology with next-generation in vivo delivery technology to establish a company named nChroma Bio, redefining the future of genetic medicine.At the same time of the merger, nChroma completed an oversubscribed financing round of $75 million, providing the company with additional funds.To drive its leading projects to obtain meaningful clinical data and build a robust pipeline of next-generation liver and extrahepatic targeted therapies.The company's leading projectCRMA-1001 is a liver-targeted epigenetic editing therapy with potential "best-in-class" efficacy and the ability to drive functional cures for chronic hepatitis B and D.

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References (Swipe up and down to view)

[1] CARVYKTI®▼ (ciltacabtagene autoleucel; cilta-cel) demonstrated significantly higher rates of minimal residual disease negativity compared to standard therapies in the CARTITUDE-4 study. Retrieved December 11, 2024, from https://www.globenewswire.com/news-release/2024/12/10/2994233/0/en/CARVYKTI-ciltacabtagene-autoleucel-cilta-cel-demonstrated-significantly-higher-rates-of-minimal-residual-disease-negativity-compared-to-standard-therapies-in-the-CARTITUDE-4-study.html

[2] Beacon Therapeutics Announces Positive 3-Month Data from Phase 2 DAWN Trial of laru-zova (AGTC-501) in Patients with X-Linked Retinitis Pigmentosa (XLRP). Retrieved December 6, 2024, from https://www.prnewswire.com/news-releases/beacon-therapeutics-announces-positive-3-month-data-from-phase-2-dawn-trial-of-laru-zova-agtc-501-in-patients-with-x-linked-retinitis-pigmentosa-xlrp-302324627.html

[3] Protara Announces Positive Results from the Ongoing Phase 2 ADVANCED-2 Trial of TARA-002 in Patients with NMIBC. Retrieved December 5, 2024, from https://www.globenewswire.com/news-release/2024/12/05/2992222/0/en/Protara-Announces-Positive-Results-from-the-Ongoing-Phase-2-ADVANCED-2-Trial-of-TARA-002-in-Patients-with-NMIBC.html

[4] Arcellx Announces New Positive Data for Its iMMagine-1 Study in Patients With Relapsed or Refractory Multiple Myeloma to be Presented During an Oral Presentation at the 66th ASH Annual Meeting and Exposition. Retrieved December 12, 2024, from https://ir.arcellx.com/news/news-details/2024/Arcellx-Announces-New-Positive-Data-for-Its-iMMagine-1-Study-in-Patients-With-Relapsed-or-Refractory-Multiple-Myeloma-to-be-Presented-During-an-Oral-Presentation-at-the-66th-ASH-Annual-Meeting-and-Exposition/default.aspx

[5] Poseida Therapeutics Highlights Positive Interim Phase 1 Results for P-BCMA-ALLO1 and Preclinical Data for Dual CAR-T P-CD19CD20-ALLO1 at the 66th American Society of Hematology (ASH) Annual Meeting. Retrieved December 12, 2024, from https://www.prnewswire.com/news-releases/poseida-therapeutics-highlights-positive-interim-phase-1-results-for-p-bcma-allo1-and-preclinical-data-for-dual-car-t-p-cd19cd20-allo1-at-the-66th-american-society-of-hematology-ash-annual-meeting-302325606.html

[6] Lyell Presents Positive Initial Clinical Data from the Phase 1-2 Clinical Trial of IMPT-314 for the Treatment of B-cell Lymphoma at the 2024 ASH Annual Meeting. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/10/2994158/0/en/Lyell-Presents-Positive-Initial-Clinical-Data-from-the-Phase-1-2-Clinical-Trial-of-IMPT-314-for-the-Treatment-of-B-cell-Lymphoma-at-the-2024-ASH-Annual-Meeting.html

[7] Synthekine Presents Positive Initial Results from Phase 1 Clinical Trial of CD19 CAR-T (SYNCAR-001) and Orthogonal IL-2 (STK-009) Combination Therapy for Treatment of Hematologic Malignancies at ASH 2024 Annual Meeting. Retrieved December 12, 2024, from https://www.synthekine.com/news/synthekine-presents-positive-initial-results-from-phase-1-clinical-trial-of-cd19-car-t-syncar-001-and-orthogonal-il-2-stk-009-combination-therapy-for-treatment-of-hematologic-malignancies-at-ash-2/

[8] AAVantgarde presents safety data of the LUCE-1 study of AAVB-081 for RP related to Usher 1B. Retrieved December 12, 2024, from https://www.aavantgarde.com/en/news/aavantgarde-presents-safety-data-of-the-luce-1-study-of-aavb-081-for-rp-related-to-usher-1b/

[9] Neurona Therapeutics Presents Positive Clinical Update: New Data from NRTX-1001 Cell Therapy Trial in Drug-resistant Epilepsy Announced at 2024 Annual Meeting of the American Epilepsy Society. Retrieved December 12, 2024, from https://www.neuronatherapeutics.com/news/press-releases/120624/

[10] IN8bio Reports Continued Progression-Free Survival in Phase 1 Investigator-Sponsored Trial of INB-100 Allogeneic Gamma-Delta T Cells for Leukemias at the 2024 American Society of Hematology Annual Meeting. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/10/2994365/0/en/IN8bio-Reports-Continued-Progression-Free-Survival-in-Phase-1-Investigator-Sponsored-Trial-of-INB-100-Allogeneic-Gamma-Delta-T-Cells-for-Leukemias-at-the-2024-American-Society-of-H.html

[11] CRISPR Therapeutics Presents Data at the 2024 American Society of Hematology (ASH) Annual Meeting. Retrieved December 12, 2024, from https://www.globenewswire.com/news-release/2024/12/09/2993974/0/en/CRISPR-Therapeutics-Presents-Data-at-the-2024-American-Society-of-Hematology-ASH-Annual-Meeting.html

[12] Chroma Medicine and Nvelop Therapeutics Unite to Form nChroma Bio, Securing $75 Million to Accelerate Genetic Medicines. Retrieved December 12, 2024, from https://chromamedicine.com/2024/12/10/chroma-medicine-and-nvelop-therapeutics-unite-to-form-nchroma-bio-securing-75-million-to-accelerate-genetic-medicines/

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