CGTLive's Pillars of Progress 2023: Top News in Oncology

For all of 2023, the CGTLive^™ team was following along the clinical development of targeted and novel engineered approaches to the treatment of patients with various medical disorders. These efforts included holding in-depth conversations with experts in the clinical care of these individuals, as well as in cell and gene therapy development, culminating in our coverage of each step of progress that the most exciting cellular and genetic treatments have made along the pipeline.

From major data publications and presentations to FDA decisions and major medical meetings, the team spent all year bringing the latest information to the website's front page.

Among our areas of focus in 2023 has been oncology, the field where chimeric antigen receptor T-cell (CAR-T) therapies first saw success. Although there were no FDA approvals of new CAR-T therapies this year, many new engineered cell therapies in the pipeline generated promising data in clinical trials. The major news items appeared among the top pieces our team produced—but sometimes smaller stories reach those heights as well because of their clinical impact, their inventive mechanisms, or otherwise. Whatever the reason for the attention these stories got, their place here helps provide an understanding of the themes in oncology over the course of 2023.

Here, we'll highlight some of the most-read content on CGTLive's oncology page this year. Click the buttons to read further into these stories.

1. First Patient Dosed in Phase 1/1b Trial of PRGN-3007 CAR-T Cell Therapy in Solid Tumors, Hematologic Malignancies

• The trial is seeking to enroll 88 participants.
• The study has an open-label design and is enrolling in 2 parts: an initial 3+3 dose escalation in each arm followed by a dose expansion at the maximum tolerated dose.
• PRGN-3007 is an UltraCAR-T therapy that uses Precigen's nonviral gene delivery system and overnight, decentralized manufacturing process.

April 1, 2023 — The first patient has been dosed in the phase 1/1b dose-escalation and -expansion study (NCT05694364) of PRGN-3007, Precigen’s investigational and first-in-class multigenic, autologous CAR-T cell therapy, according to a company announcement. The trial is seeking to enroll 88 participants with solid tumors—including those with breast adenocarcinomas encompassing triple negative breast cancer—and patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma, acute lymphoblastic leukemia, and diffuse large B-cell lymphoma.

"We are excited to work with Precigen and announce that the first patient, a CLL patient, has been dosed in the first-in-human study of PRGN-3007 UltraCAR-T"

– Javier Pinilla-Ibarz, MD, PhD, of H. Lee Moffitt Cancer Center and Research Institute

2. Evidence of Disease Reduction Observed Among Patients Treated With Ovarian Cancer CAR-T PRGN-3005

• PRGN-3005 is an investigational MUC16-directed CAR-T therapy intended for the treatment of patients with platinum-resistant ovarian cancer.
• It is currently being assessed in a phase 1/1b clinical trial (NCT03907527).
• The CAR-T was designed with a feature expected to improve persistence with the intention of overcoming limitations that have held back the success of trials for other CAR-T therapies directed at ovarian cancer.

July 2, 2023 — Interim results from the study evaluating PRGN-3005 were presented at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois. At the conference, CGTLive™’s sister publication OncLive™, spoke with Mary “Nora” Disis, MD, director of University of Washington Medicine’s Cancer Vaccine institute, who coauthored the study, about the key findings and their potential implications for the solid tumor treatment landscape.

"I think that this study represents a very novel method of the delivery of CAR T-cell therapy in the sense that we literally take the blood from the patients, we transfect the cells in the blood overnight, and the next day we infuse the CAR T-cells back into the patient."

– Mary “Nora” Disis, MD, of University of Washington Medicine's Cancer Vaccine Institute

3. CARTITUDE-4 Data Leak Reveals Promising Results for Cilta-Cel in Multiple Myeloma

• Based on the data that were obtained, those treated with the chimeric antigen receptor T-cell (CAR-T) therapy—also known as cilta-cel—reported a 74% reduction in the risk of disease progression compared with standard regimens.
• Carvykti is reported to have cut the mortality risk by 22% relative to standard chemotherapy, though this effect appears to have been deemed not statistically significant.
• The trial has an estimated completion date of April 10, 2026.

April 19, 2023 — Among individuals with relapsed and lenalidomide-refractory multiple myeloma (MM), ciltacabtagene autoleucel (Carvykti; Johnson & Johnson/Legend Biotech) has outperformed expectations compared with standard chemotherapy regimens—such as pomalidomide, bortezomib and dexamethasone; or daratumumab, pomalidomide and dexamethasone—according to leaked data from the phase 3 CARTITUDE-4 trial (NCT04181827) obtained by STAT News.

4. Janssen No Longer Seeking Approval for Carvykti in the UK

• According to Myeloma UK, the withdrawal was not related to any safety or efficacy concerns.
• The decision was likely related to production issues which have affected the ability of manufactures to meet demand for CAR-T therapies, which are more complex to produce than many other types of cancer treatments.
• The group noted that manufacturing issues have affected the availability of CAR-T therapies developed by other companies, including Bristol Myers Squibb’s ide-cel.

March 17, 2023 — Janssen is no longer seeking the approval of ciltacabtagene autoleucel (cilta-cel; Carvykti), a CAR-T therapy for the treatment of relapsed/refractory MM, by the UK’s National Institute of Health and Care Excellence (NICE), according to the charity group Myeloma UK. Carvykti, which was approved in the United States in 2022, was in the process of being evaluated by NICE.

“Despite our efforts and commitment to advancing this cell therapy for patients and physicians, we are not currently in a position to progress through the NICE appraisal process.”

– Brian Kenney of Janssen

5. Metastatic Colorectal Cancer Therapy CAR-T GCC19CART Improves Upon Third-Line SOC Therapies

• Among the 21 patients included in the efficacy analysis, superior results were observed in patients (n = 8) who received the higher dose level (2x10⁶ CAR-T cells/kg; DL2) than in patients (n = 13) who received the lower dose level (1x10⁶ CAR-T cells/kg; DL1).
• The objective response rate (ORR) was 50% (n = 4) for DL2, 15% (n = 2) for DL1, and 29% (n = 6) for all patients.
• Meanwhile, the median overall survival (OS) for DL2 was not reached with a median followup of 20.02 months, while the median OS for DL1 was 13.32 months; the overall median OS was also not reached.

April 19, 2023 — GCC19CART (Innovative Cellular Therapeutics), an investigational autologous CAR-T therapy being evaluated in an investigator-initiated clinical trial (ChiCTR2000040645) in China for the treatment of relapsed/refractory metastatic colorectal cancer (mCRC), has demonstrated efficacy improvements over standard of care (SOC) third-line therapies, according to data presented at the American Association for Cancer Research (AACR) Annual Meeting 2023, held April 14-19, 2023, in Orlando, Florida.

“Most patients treated with this product experienced diarrhea, but it can be controlled and because of the diarrhea management most of the patients actually recovered very quickly.”

– Victor Lu, PhD, of Innovative Cellular Therapeutics