Arcellx, Gracell Biotechnologies, and Oricell have demonstrated impressive clinical outcomes at ASCO 2022, posing a challenge to J&J/Legend Biotech’s and BMS's leading CAR-T cell therapies.
Abstract Number #8003:
Arcellx presented the latest findings on CART-ddBCMA, its BCMA-specific CAR-modified T-cell therapy for multiple myeloma, at the ASCO 2022. The preliminary CART-ddBCMA clinical data at the cutoff date of May 3, 2022, show profound and long-lasting responses in individuals with poor prognostic characteristics. According to the International Myeloma Working Group criteria, a 100% overall response rate (ORR) was obtained in all 31 evaluable patients with a median follow-up of 12.1 months. Complete response (CR) or a stringent complete response (sCR) was obtained by 71% of evaluable patients. At least 94% of patients had a very good partial response (VGPR). A partial response (PR) was observed in 6% of patients with a median follow-up of 17.7 months, 81% of individuals dosed more than a year ago achieved CR/sCR, while 56% remain in continuous response. CART-ddBCMA at RP2D (100 million CAR+T cells) was well tolerated. Toxicities such as CRS and Immune Effector Cell Associated Neurotoxicity (ICANS) were manageable and resolved with normal treatment at both dosage levels. There were no reports of delayed neurotoxicity episodes or parkinsonian symptoms. There were no grade 3 (or higher) CRS cases and just one case (4%) of grade 3 ICANS event, with no new cases from previously reported cases.
Abstract Number #8004:
OriCell also presented data from the OriCAR-017 Phase I POLARIS project in an oral presentation at the ASCO Annual Meeting 2022. In heavily pretreated relapsed/refractory multiple myeloma patients, a single infusion of OriCAR -017 demonstrates early, deep, and durable responses at all dose levels. According to the data, the ORR was 100%, with a CR/sCR rate of 60%. At the time of the data cutoff, all patients had not progressed and were not receiving any further therapy. There were no Dose Limiting Toxicities (DLTs) or Serious Adverse Events (SAEs). There were no ICANS and just Grade 1/2 CRS. The most prevalent Grade 3/4 AE was cytopenia, mostly caused by lymphodepleting chemotherapy.
Abstract Number #8005:
The data presented at ASCO suggests that GC012F produced an 83% ORR among 28 patients. All 27 patients evaluable for MRD status were negative, and 87.5% of eight patients evaluable at 12 months were MRD-negative. In addition, the longest ongoing responses are more than 29 months old.
"We are excited by these long-term results, particularly given the challenging patient demographics, and believe these promising results reflect the potential for our lead program, CART-ddBCMA, to be a best-in-class treatment for patients with multiple myeloma," Expert Opinion.
"We are delighted to share the First-in-Human data from our Phase I POLARIS study, we strongly believe these data has demonstrated our advantages from the proprietary platforms for CAR-T optimization structure. Next step, we will be focusing on filing an IND with the NMPA and FDA for Ori-CAR017."–Expert Opinion
"GC012F is the first dual-targeting CAR-T with clinical data in RRMM, which is designed to improve depth of response as well as tackling some of the major challenges of CAR-T therapy, including the need for faster delivery to the patients in need”.–Expert Opinion
CAR-T cell therapies have emerged as a new therapeutic option for hematologic cancers such as High-grade B-cell lymphoma (HGBL), Diffuse large B-cell lymphoma (DLBCL), Follicular lymphoma (FL), Mantle cell lymphoma, primary mediastinal B-cell lymphoma (PMBCL), Multiple myeloma, and Acute lymphoblastic leukemia (ALL). The United States Food and Drug Administration (FDA) has already approved Bristol Myers Squibb’s (Abecma [idecabtagene vicleucel]) and Johnson & Johnson's (Carvykti [ciltacabtagene autoleucel]) CAR-T cell therapy for Multiple Myeloma. While this therapeutic strategy has many advantages, it does have some downsides, such as the long manufacturing process, potential side effects, and high cost. Manufacturing these therapies takes time, and companies sometimes barely keep up with demand, thus limiting their use. For example, BMS's Abecma is experiencing supply problems and is struggling to meet demand. Not only that, but the approved CAR-T cell treatments come with black box warnings. These issues indicate that patients and healthcare providers must have a variety of treatment options. Many companies are now investigating CAR-cell therapies, and preliminary results have been promising. Small biotech companies Arcellx, Gracell Biotechnologies, and Oricell are actively going forward with their CAR-T cell therapies in an attempt to take market share away from the larger companies.
Arcellx’s BCMA-targeted CAR-T therapy, known as CART-ddBCMA, is coming behind already approved ones from Janssen and BMS. The results reported at ASCO 2022 are quite similar to J&J's CAR-T program. It is worth mentioning that Arcellx’s CART-ddBCMA has been granted Fast Track Designation, Orphan Drug Designation, and Regenerative Medicine Advanced Therapy Designation by the US FDA for the treatment of relapsed/refractory multiple myeloma. And, the company is planning to initiate a Phase II pivotal study year-end 2022. Gracell is exploring CAR-T that targets both CD19 and BCMA, i.e., GC012F. The company plans to file an Investigational New Drug (IND) in the United States and China for GC012F to treat relapsed/refractory multiple myeloma during the second half of 2022. Multiple myeloma BCMA targeted rivals are increasing, and competition has begun to intensify. Thus, companies are exploring CAR-T cell therapies with other novel targets. OriCAR017 is a GPRC5D CAR-T cell therapy being developed by ORIcell. The rivalry in the GPRC5D space is there; however, it is not as extensive as in other targets. J&J's bispecific-antibody talquetamab is certainly the most advanced GPRC5D-targeting drug in Multiple Myeloma.
The abovementioned investigational therapies are showing promise in Multiple Myeloma. Yet, one cannot overlook the fact that J&J's Carvykti will fight them tooth and nail, as Carvykti already has an efficacy advantage over Abecma as well. The company has revealed strong data from the Cartitude-1 and Cartitude-2 studies at ASCO 2022. Data from the Cartitude-2 research presented at ASCO 2022 indicate that this therapy has the potential to extend into earlier lines. These findings represent a significant step forward for CAR-T cell treatments in the relapsed/refractory scenario. So, the long-lasting response rate and good safety are what matter in the end. The safety efficacy data must be strong enough to convince patients and physicians.
Companies- Oncopeptides, GlaxoSmithKline, Bluebird Bio, Janssen Pharmaceutical, Legend Biotech, AbbVie, Roche (Genentech), Bristol Myers Squibb, Regeneron Pharmaceuticals, Pfizer, Takeda, Amgen, SpringWorks Therapeutics, Arcellx, Gracell Biotechnologies, Oricell, Poseida Therapeutics, Precision Biosciences, CRISPR Therapeutics AG, Collectis SA, Allogene Therapeutics, Fortis Therapeutics, Novartis, I-Mab/MorphoSys, Cartesian Therapeutics, CASI Pharmaceuticals, LAVA Therapeutics, and others