Dr Weinkove is Clinical Director at the Malaghan Institute of Medical Research (MIMR), and holds a joint appointment as a Consultant Haematologist at Wellington Blood & Cancer Centre. After studying medicine at the University of Cambridge and Kings College London, he trained in haematology at Guy's and St Thomas' Hospitals in London and the Medizinische Hochschule Hannover. He was awarded a PhD from the University of Otago in 2012.
Dr Weinkove is a key member of the Cancer Immunotherapy Programme at MIMR, where he is leading a chimeric antigen receptor (CAR) T-cell programme. Under Medsafe license, MIMR's dedicated Good Manufacturing Practice facility has established clinical-grade lentiviral (LV) vector and CAR T-cell production. Dr Weinkove is Principal Investigator for ENABLE, a phase I study of a new third-generation CAR T-cell for relapsed and refractory B-cell lymphoma.
As New Zealand's first CAR T-cell trial, ENABLE has required establishment of new manufacturing, regulatory and clinical processes and procedures. Dr Weinkove recently took up a Clinical Practitioner Research Fellowship from the Health Research Council, with the goal of leveraging this experience to facilitate New Zealand participation in other investigator-initiated and commercial CAR T-cell trials, and accelerating future adoption of this new cancer immunotherapy.
Chimeric antigen receptor t-cells: the enable trial
Patient T-cells can be genetically modified to express a chimeric antigen receptor (CAR) targeting malignant cells. CAR T-cell therapies are licensed for relapsed and refractory B-cell non-Hodgkin lymphomas (r/r B-NHL). However, while ˜ 40% of CAR T-cell recipients enter durable remission, most do not respond fully, or relapse.
The Malaghan Institute is manufacturing a new anti-CD19 CAR T-cell ('WZTL-002'), incorporating a Toll-like receptor 2 domain. Preclinically, this has improved cytotoxicity against B-cells, and clinical data from a linked trial suggests comparable toxicity profile, at lower dose, than licensed products.
ENABLE is a phase 1 dose escalation trial. Eligible participants are adults with r/r B-NHL, lack curative options and have satisfactory organ function. Following enrolment, participants undergo leukapheresis. Following CAR T-cell manufacture, lymphodepleting chemotherapy precedes a single dose of WZTL-002. The primary endpoint is safety. Secondary endpoints are feasibility, overall response rate at 3 months, cumulative complete response rate at 6 months, relapse-free and overall survival at 24 months, and recommended phase 2 dose.
Our local CAR T-cell and vector manufacturing capability should enable further early-phase trials. The regulatory approvals and protocols established may enable NZ participation in co-operative group and commercial trials, and help prepare for this emerging cancer immunotherapy.