SAN JOSE & SAN FRANCISCO, CALIF., U.S., NANJING & SHANGHAI CHINA, Dec. 13, 2021 – IASO Biotherapeutics (“IASO Bio”), a clinical-stage biopharmaceutical company focused on discovering, developing, and manufacturing innovative medicines and Innovent Biologics, Inc. (“Innovent”, HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, today jointly announced the latest data from the phase 1/2 clinical study of a fully human B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy in an oral presentation at the 63rd American Society of Hematology (ASH) Annual Meeting (Abstract # 547). BCMA CAR-T therapy was co-developed by the two companies (IASO Bio: CT103A, Innovent: IBI326) for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). Presentation title: A Phase 1/2 Study of a Novel Fully Human B-Cell Maturation Antigen-Specific CAR T Cells (CT103A) in Patients with Relapsed and/or Refractory Multiple Myeloma with Professor Chunrui Li, MD, PhD, from Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology (HUST) in China as the oral presenter.
The updated data is based on a single-arm, open-label, multi-center phase 1/2 study being conducted in China. The study mainly enrolled patients with BCMA-positive RRMM who had an Eastern Cooperative Oncology Group (ECOG) performance score of 0-1 and received ?3 lines of prior therapy. The study’s primary endpoint is objective response rate (ORR), with secondary endpoints including duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, tolerability, pharmacokinetics and pharmacodynamics (PK/PD). As the data cutoff date of Oct.12, 2021, this study included 79 subjects treated with the recommended Phase II dose (RP2D) of 1.0×106 CAR-T cells/kg (9 from the exploratory investigator-initiated trial [IIT] and 70 from the registrational study [Trial Registration# NCT05066646]).
Study results showed that CT103A has excellent safety and efficacy profiles, as corroborated by long in vivo persistence, indicating that CT103A has the potential to be a breakthrough therapy for patients with RRMM.
CT103A demonstrated a favorable and manageable safety profile: Among the 79 patients, 75 (94.9%) experienced cytokine release syndrome (CRS). The majority of them experienced 1~2 CRS; only 2 experienced grade 3 CRS (all occurred during the IIT phase of the study, while the 70 patients in the registrational study did not report any grade 3 or higher CRS). The median time to CRS onset was 6.0 days after infusion, and the median duration of CRS was 5.0 days. Only 1 patient experienced grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) manifested as transient decrease in consciousness and soon resolved without intervention. All patients with CRS or ICANS have resolved, among which 20% and 34.7% were treated with tocilizumab and steroids respectively.
CT103A showed favorable and durable efficacy: Of the 79 patients, the ORR was 94.9% and the complete response/stringent complete response (CR/sCR) rate was 58.2%, with a trend suggesting a correlation between deeper responses and longer follow-ups. PFS at 6, 9, and 12 months after infusion was 78.0%, 76.0%, and 71.0%, respectively. CT103A also demonstrated favorable efficacy in 11 patients with EMM, achieving an ORR of 100% and a CR/sCR rate of 72.7%. In all 79 patients, 93.7% achieved minimal residual disease (MRD)-negativity with a sensitivity of 10-5 at least once after infusion.
CT103A also demonstrated favorable efficacy in patients who had received prior CAR-T therapy: Among the 13 patients who previously received CAR-T therapy, the ORR was 76.9%, with 61.5% of those patients achieving very good partial response (VGPR) or deeper responses, and 46.2% achieved CR/sCR.
CT103A demonstrated robust expansion and prolonged persistence: The expansion of CT103A in peripheral blood reached the peak at a median of 12 days, with a median Cmax of 92,000 copies/ug DNA. CT103A was still detectable in 10 (55.6%) of the 18 patients who completed 12-month follow-up after infusion. The first enrolled patient still had detectable CT103A transgene (4,040 copies/ug DNA) 34 months (1,030 days) after infusion, and remained in sCR during this time. Soluble BCMA in peripheral blood of patients rapidly declined after CT103A infusion and persistently remained below the detectable limit.
CT103A has low immunogenicity: Only 1.3% (1/79) of patients were tested anti-drug antibody (ADA)-positive within three months after CT103A infusion. At a median follow-up duration of seven months, only 12.7% (10/79) of patients tested ADA-positive.
“While a high rate of relapse remains a major clinical challenge in RRMM, BCMA-targeted CAR-T has thus far showed great promise in its treatment. CT103A is a fully-human BCMA-specific CAR-T therapy that can reduce relapse by bypassing potential anti-CAR immunogenicity in the host. This CT103A study demonstrated favorable efficacy, safety, PK/PD, and low immunogenicity, signifying enormous therapeutic value for the treatment of RRMM as potentially a clinical breakthrough,” said the two principal investigators at the primary centers of the study – Prof. Lugui Qiu, MD, from the Chinese Academy of Medical Science Hematology Hospital and Prof. Chunrui Li, MD, PhD, from Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology.
Dr. Wen (Maxwell) Wang, Chief Executive Officer and Chief Medical Officer of IASO Bio, said: “This is our second time reporting CT103A results during an oral session at ASH Meeting. And this year’s new data for safety and efficacy of CT103A is particularly exciting. It includes some of the results from the registrational study at 11 sites which is worth emphasizing since it’s globally the first registrational study that enrolled patients who had failed prior CAR-T treatment. For these patients, who have no approved treatment options, CT103A also demonstrated favorable and durable efficacy, once again highlighting the enormous therapeutic potential of this innovative candidate. At present, we are also advancing the clinical development of CT103A for early-line treatments, combination therapies and autoimmune diseases, while expanding the development program globally. We’ll submit the new drug application (NDA? soon and look forward to launching this cell therapy to benefit even more patients in the future. ”
Dr. Hui Zhou, Senior Vice President of Innovent, said: “Multiple myeloma (MM) is a common hematology malignant disease with high incidence rate, and relapse and refractory are inevitable after current treatments. There’s an urgent unmet need requesting a treatment with well-tolerated and long persistence for patients. We are glad the results from the Phase I/II study of CT-103A (Innovent R&D code: IBI326) were announced in an oral presentation at this year’s ASH Annual Meeting. These results looks very promising as they have demonstrated favorable and durable efficacy and manageable efficacy of IBI326. We will further accelerate this clinical development of IBI326 to bring forth a treatment option that will bring new hope to patients with MM.”