Talicabtagene autoleucel for relapsed or refractory B-cell malignancies: an open-label, multicentre, phase 1/2 study
The trial report behind India's first CAR-T therapy: about three in four heavily pretreated patients with lymphoma or leukaemia responded to cells engineered and made in Mumbai.
Overview
Open-label phase 1/2 study at six Indian tertiary centres enrolling 64 patients (14 phase 1, 50 phase 2) with relapsed or refractory B-cell lymphoma or B-ALL; phase 2 dose at least 5 x 10^6 CAR-T cells per kg (up to 2 x 10^9). Among 51 efficacy-evaluable patients (36 lymphoma, 15 B-ALL) the overall response rate was 73% (37 of 51; 95% CI 59-83). Grade 3 or worse neutropenia (96%), thrombocytopenia (65%) and anaemia (61%) were common; two deaths were treatment related. An accompanying commentary framed the approval as a model for CAR-T in lower-income countries.
- Overall response rate 73% (37 of 51 evaluable patients).
- Grade 3 or worse neutropenia in 96%, thrombocytopenia 65%, anaemia 61%.
- Two treatment-related deaths (one with haemophagocytic lymphohistiocytosis and septic shock, one pulmonary bleed with cytokine release syndrome).
- Product manufactured domestically with a humanised CD19 binder; approved by the DCGI in 2023.
A lower-middle-income country can design, manufacture, trial and approve an autologous CAR-T therapy. Response rates are in the range of first-generation Western products in similar mixed populations, at a price an order of magnitude lower, which reopens the question of what CAR-T should cost everywhere.
- Single-arm, small, mixed histologies; durability data are short.
- Response assessment and comparability to pivotal Western trials (which used disease-specific cohorts and complete response endpoints) are limited.
- Haematological toxicity was very high and two deaths were treatment related; safety systems at 130-plus centres matter.
Pages like this
not linked directly; found by shared links- IdeaPublic-sector CAR-T manufacturing in India, Brazil and South Africa under $50,000
Shares Talicabtagene autoleucel, Tata Memorial Centre, Manufacturing cost and time for living and radioactive medicines, Most of the world has almost no cancer care.
- InstitutionAdvanced Centre for Treatment, Research and Education in Cancer
Shares Indian Institute of Technology Bombay, Talicabtagene autoleucel (NexCAR19) phase 1/2, ImmunoACT, Talicabtagene autoleucel.
- CompanyCipla
Shares ImmunoACT, Talicabtagene autoleucel, Most of the world has almost no cancer care, CAR-T cell therapy.
- ProductVarnimcabtagene autoleucel
Shares Talicabtagene autoleucel, Manufacturing cost and time for living and radioactive medicines, Most of the world has almost no cancer care, Acute lymphoblastic leukaemia.
- TechnologyPoint-of-care and decentralised cell manufacturing
Shares Rahul Purwar, Indian Institute of Technology Bombay, ImmunoACT, Talicabtagene autoleucel.
- InstitutionDepartment of Biotechnology, Government of India
Shares Indian Institute of Technology Bombay, ImmunoACT, Manufacturing cost and time for living and radioactive medicines, CAR-T cell therapy.
- TrialIMAGINE (varnimcabtagene autoleucel, Immuneel)
Shares Manufacturing cost and time for living and radioactive medicines, Most of the world has almost no cancer care, Acute lymphoblastic leukaemia, Diffuse large B-cell lymphoma.
- CompanyCellogen Therapeutics
Shares Manufacturing cost and time for living and radioactive medicines, Acute lymphoblastic leukaemia, Diffuse large B-cell lymphoma, CAR-T cell therapy.