- Source : Press Release
- Date : 2021-12-07
- Event type : Phase 1
- Companies : Immunocore Holdings plc, Roche
Immunocore Announces Initial Phase 1 Data of ImmTAC Candidate IMC-C103C Targeting MAGE-A4
Clinical activity with confirmed durable responses in ovarian cancer and a confirmed durable response in HNSCC
Manageable safety profile
Biomarkers of T cell activation consistent and robust at doses ≥ 90 micrograms
First expansion in high grade serous ovarian cancer initiated
OXFORDSHIRE, UK & CONSHOHOCKEN, PA & ROCKVILLE, MD, USA I December 6, 2021 IImmunocore Holdings Plc (Nasdaq: IMCR), a late-stage biotechnology company pioneering the development of a novel class of T cell receptor (TCR) bispecific immunotherapies designed to treat a broad range of diseases, including cancer, infectious and autoimmune disease, today announces the initial Phase 1 data of IMC-C103C, a bispecific T cell engager targeting MAGE-A4, in selected advanced solid tumors.
IMC-C103C was developed using the company's innovative ImmTAC® technology platform and is being developed in partnership with Genentech, a member of the Roche Group. The trial (IMC-C103C-101) includes a Phase 1 dose escalation to evaluate safety, maximum tolerated dose / expansion dose, and preliminary clinical activity. The initial Phase 1 data from this study is the subject of a presentation at the European Society of Medical Oncology Immuno-Oncology Congress.
The presentation includes data from 44 patients enrolled across 10 dose-escalation cohorts. Indications with high MAGE-A4 prevalence (eg. serous ovarian, synovial sarcoma) enrolled all-comers with retrospective MAGE-A4 testing by immunohistochemistry (IHC) while other indications required prospective confirmation of tumor MAGE-A4 expression by IHC.
IMC-C103C demonstrated a manageable safety profile. The most common any-grade, treatment-related adverse events were consistent with cytokine release syndrome, were dose dependent and rapidly resolved. The most common related grade 3 or grade 4 adverse event was neutropenia, typically at doses ≥ 90 micrograms. Neutropenia was reversible, with treatment interruption or G-CSF, and was not dose-limiting. None of the treatment-related AEs led to discontinuation or death.
IMC-C103C dose escalation began at 0.5 micrograms, the minimum anticipated biological effect level (MABEL), and includes 10 cohorts to date. Pharmacodynamic biomarkers of T cell activation were first observed at 15 micrograms and became consistent and robust at doses ≥ 90 micrograms. IMC-C103C treatment results in a substantial increase in T cell infiltration in tumor biopsies relative to baseline.
The most frequently enrolled patients had platinum relapsed/refractory ovarian cancer, who were enrolled regardless of their tumor MAGE-A4 protein expression. Most of these patients had low or no MAGE-A4 protein expression in their tumors as measured by IHC (median H score = 8). One ovarian cancer patient, with a very low MAGE protein expression, treated at a dose of less than 90 micrograms, had a durable confirmed partial response (PR) with 8.3 months duration. An additional ovarian cancer patient at a dose of ≥ 90 micrograms, also with very low MAGE-A4 protein expression, has a confirmed partial response ongoing at 4.4+ months. One of the three non-ovarian cancer patients (head and neck squamous cell carcinoma) at a dose of ≥ 90 micrograms has a confirmed PR that is ongoing.
“IMC-C103C is our second T cell engager to demonstrate durable clinical activity, now in multiple solid tumors,” stated Bahija Jallal, Chief Executive Officer. “We are highly encouraged to see these responses in ovarian and head and neck cancer. The durable PRs in ovarian cancer occur in heavily pre-treated patients even with low MAGE-A4 protein tumor expression. We have initiated an expansion arm in ovarian carcinoma, while we continue signal searching and determining the optimal dose in multiple solid tumors.”
Earlier this month, Immunocore initiated an expansion arm in high grade serous ovarian carcinoma at 140 micrograms. IMC-C103C-101 will continue to explore the optimal dose and evaluate clinical activity in multiple solid tumors. The company plans to present additional data from this program in 2022. IMC-C103C is part of a co-development / co-promotion collaboration with Genentech under which Immunocore shares program costs and profits equally.
Immunocore is a late-stage biotechnology company pioneering the development of a novel class of TCR bispecific immunotherapies called ImmTAX – Immune mobilizing monoclonal TCRs Against X disease – designed to treat a broad range of diseases, including cancer, infectious and autoimmune. Leveraging its proprietary, flexible, off-the-shelf ImmTAX platform, Immunocore is developing a deep pipeline in multiple therapeutic areas, including five clinical stage programs in oncology and infectious disease, advanced pre-clinical programs in autoimmune disease and multiple earlier pre-clinical programs. Immunocore's most advanced oncology therapeutic candidate, tebentafusp, has demonstrated an overall survival benefit in a randomized Phase 3 clinical trial in metastatic uveal melanoma, a cancer that has historically proven to be insensitive to other immunotherapies.