Data Roundup: August 2024 Features Updates in CAR-T, mRNA Therapy, and Gamma Delta T-cell Therapy for Various Cancers

Last month, August 2024, the CGTLive® team was diligently tracking the latest data readouts and published literature on cell and gene therapies within oncology, neurology, rare diseases, and more.

As more and more innovative therapies enter the clinical trial field, more data is accrued every month, buoying excitement in the field and sometimes making or breaking the fates of small biotech companies. Last month delivered promising data updates in chimeric antigen receptor T-cell (CAR-T) therapy, mRNA therapy, and gamma delta T-cell (GDT) therapy for various solid and liquid cancers. Our team has highlighted these updates below.

Click the read more buttons for more details and information about each update.

New Study Recommends Shorter, Flexible Monitoring After CAR T-Cell Therapy

August 1, 2024 - A new study published in Blood Advances has found that a shorter, flexible monitoring period after CAR T-cell therapy beyond 14 days appears safe and feasible and may help to improve access to these therapies.

The new research, conducted by first author Nausheen Ahmed, MD, Associate Professor, Hematologic Malignancies and Cellular Therapeutics, and Assistant Director, Cellular Therapeutics, and Medical Director, BMT Survivorship Program, University of Kansas Medical Center, and colleagues found that instances of new-onset cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are rare after 14 days.

“As a clinician that administers CAR-T, I’ve had many patients who have not been able to receive it because of barriers to access,” Ahmed said in a statement. “I have patients who are traveling for 6 or even 8 hours to get treatment."

mRNA Therapy/Anti-PD-L1 Therapy Combo Meets Primary Endpoint in ORR Over Historical Control

August 4, 2024 - BioNTech’s phase 2 clinical trial (NCT04526899) evaluating BNT111 mRNA therapy in participants with unresectable stage III or IV melanoma whose disease had progressed following anti-PD-L1 therapy has met its primary endpoint.

The therapy demonstrated a statistically significant improvement in overall response rate (ORR) in patients treated in combination with cemiplimab, an anti-PD-1 monoclonal antibody being developed by Regeneron, as compared with historical control.

“These phase 2 results mark a significant step towards our vision of personalized cancer medicine. We envision mRNA as a centerpiece in future treatment paradigms for cancer, helping to address unmet medical needs, such as for patients with anti-PD-(L)1 refractory or resistant melanoma,” Prof. Özlem Türeci, MD, chief medical officer and cofounder, BioNTech, said in a statement. “These data are a proof of concept for us in 3 dimensions: First, for our decade-long improved mRNA cancer vaccine technology that uses uridine mRNA chemistry, a noncoding backbone that is engineered for optimal translational performance and our proprietary lipoplex formulation for delivery. Second, for our computational approaches for selecting suitable tumor antigens for our cancer indication-specific FixVac platform candidates. Third, for our strategy to combine synergistic modalities, in this case BNT111 with an established immune checkpoint treatment.”

Long-Term Axi-Cel Data Shows Durable Outcomes, Elucidates Drivers of Nonrelapse Mortality

August 8, 2024 - New, long-term research on outcomes with axicabtagene ciloleucel (axi-cel) CAR T-cell therapy has demonstrated sustained, durable response in participants with large B-cell lymphoma (LBCL) 5 years after treatment but has also called attention to issues that reduce long-term survival, particularly in elderly patients.

“Our research shows that axi-cel can provide durable, long-lasting responses in a substantial portion of patients with relapsed or refractory large B-cell lymphoma,” lead study author Michael Jain, MD, PhD, associate member, Blood and Marrow Transplant and Cellular Immunotherapy Department, Moffitt Cancer Center, said in a statement. “This is noteworthy given the limited options available for these patients previously.”

The retrospective analysis, published in Journal of Clinical Oncology, was led by Moffitt Cancer Center and included data from a consortium of 16 other US academic cancer centers. The analysis reported on 298 patients who were leukapheresed with the intent to receive standard-of-care axi-cel (n = 275 infused) after 2 or more previous lines of therapy, with extended follow-up data to a mean of 58 months.

Kiromic BioPharma’s NSCLC T-cell Therapy Deltacel Generates Favorable PFS Data in Interim Phase 1 Trial Results

August 13, 2024 - Kiromic BioPharma’s KB-GDT-01 (Deltacel), an investigational allogeneic gamma delta T-cell (GDT) therapy being evaluated in the phase 1/2 Deltacel-01 clinical trial (NCT06069570) for the treatment of non-small cell lung cancer (NSCLC), has shown favorable progression-free survival (PFS) data in an interim update from the study.

For the 5 patients in long-term follow-up who have been evaluated, the average PFS is 4.8 months (range, 2-8 months). In terms of safety, Kiromic noted that there were no dose-limiting toxicities among the patients who were treated with a full course of Deltacel in the trial. Although, 1 patient experienced an adverse event deemed related to a preexisting comorbidity, but not to Deltacel, and subsequently ceased participation in the trial without having completed a full course of Deltacel. This patient was not able to be evaluated for PFS. All patients treated so far have been treated in Part 1 of Deltacel-01, which is the dose escalation portion. The sixth patient in Part 1, who started receiving Deltacel on August 6, 2024, is the final patient that Kiromic intends to treat in Part 1. Part 1 includes 2 cohorts of 3 patients each.

The company noted that it expects to provide initial safety results from the aforementioned sixth patient in September and initial efficacy results for that patient in October. In July 2024, Kiromic reported that it intends to move to Part 2 of Deltacel-01, noting that the trial’sSafety Monitoring Committee had given a positive assessment. Part 2 of the study, which will constitute a dose expansion portion, is expected begin in September, as well.

Orgenesis’ CAR-T ORG-101 Demonstrates Efficacy and Safety in Acute Lymphoblastic Leukemia in Real-World Study in China

August 30, 2024 - Orgenesis’ ORG-101, a CD19-directed CAR-T therapy, has demonstrated efficacy and safety in patients with CD19+ B-cell acute lymphoblastic leukemia (ALL) treated in real-world data that came from 233 patients treated at a leading hematology center in China.

Among the treated patients, the complete response (CR) rate in adults was 82% and the CR rate in children was 93%. In terms of safety, severe CRS was observed in 2% of treated adults and 6% of treated children. Orgenesis stated that these severe CRS rates are low in comparison to approved CAR-T treatments.

ORG-101, which is produced with a third-generation lentiviral vector coding for a proprietary CAR construct, is manufactured and undergoes analytic testing onsite via a decentralized approach that differs from the centralized approach to manufacturing used for a “traditional” CAR-T therapies. Orgenesis notes that it has held meetings on the topic of ORG-101 with the FDA, the Ministry of Health of Israel, and Germany's Paul-Ehrlich-Institute, and that it intends to bring ORG-101 into a multicenter phase 1/2 clinical trial. With the support of its Enterprise Greece Grant, it will aim to use General University Hospital of Patras in Greece as the first site for the trial.