Phase 1 trial enrolled all comers, with vast majority of patients having zero or very low
MAGE-A4 expression
IMC-C103C has a manageable safety profile and demonstrated signals of clinical activity
The RECIST response rate was low in the population with zero or very low MAGE-A4 expression
ctDNA reductions observed even at low MAGE-A4 expression
OXFORDSHIRE, UK & CONSHOHOCKEN, PA & ROCKVILLE, MD, USA I December 08, 2022 I Immunocore Holdings plc (Nasdaq: IMCR), a commercial-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, autoimmune and infectious diseases, today presented data for IMC-C103C, a bispecific T cell engager targeting MAGE-A4, in patients with ovarian cancer.
The Phase 1 data, presented in a poster at the ESMO Immuno-Oncology 2022 Congress, include 33 heavily pre-treated patients with ovarian cancer, who received doses of ≥ 90 mcg intravenously. This includes 16 new patients, and 17 patients previously reported at the ESMO Immuno-Oncology 2021 Congress, now with longer follow-up. All patients had platinum relapsed/refractory ovarian cancer (70% PARP inhibitors experienced) and were enrolled regardless of MAGE-A4 protein expression, which was analyzed retrospectively.
Of the 33 patients, 39% (13/33) were MAGE-A4 negative as measured by immunohistochemistry (IHC), and 2 patients had an unknown H score. Of the 55% (18/33) MAGE-A4 positive patients, the majority had low expression (median score = 29 of 300), and only 2 had an H score > 150.
The safety profile was consistent with that reported previously and the mechanism of action, i.e., T cell activation. No related AE led to treatment discontinuation or death.
At the time of data cut-off, 32 patients were evaluable for response, with one additional patient (H score 21) still on treatment and not having had first tumor assessment. Of the 17 evaluable MAGE-A4 positive patients, one had a durable Partial Response (PR), with a duration of 12.7 months, one patient who had a Stable Disease (SD) converted to an unconfirmed PR after the poster data cutoff date and is still ongoing, and 5 had SD. Reductions in ctDNA were observed in over half of ctDNA evaluable patients (12/22), including 7 with ≥ 50% reductions, and even in those with low or zero MAGE-A4 expression.
“Immunocore has learned from tebentafusp that OS benefit and ctDNA reduction are observed in patients with both high and low total protein expression, while RECIST responses are enriched at higher protein expression,” said David Berman, Head of Research and Development of Immunocore. “The emerging IMC-C103C results, where most patients had either no or very low MAGE-A4 expression, are consistent with the RECIST and ctDNA reduction results reported for tebentafusp.”
IMC-C103C is part of a co-development / co-promotion collaboration with Genentech, a member of the Roche Group under which Immunocore shares program costs and profits equally. Both companies are evaluating next steps for the IMC-C103C program.
About Immunocore
Immunocore is a commercial-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, autoimmune, and infectious disease. 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 TCR therapeutic, KIMMTRAK, has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM) in the United States, European Union, Canada, Australia and the United Kingdom, having demonstrated an overall survival benefit in a randomized Phase 3 clinical trial in mUM, a cancer that has historically proven to be insensitive to other immunotherapies.
SOURCE: Immunocore
Post Views: 516
Phase 1 trial enrolled all comers, with vast majority of patients having zero or very low
MAGE-A4 expression
IMC-C103C has a manageable safety profile and demonstrated signals of clinical activity
The RECIST response rate was low in the population with zero or very low MAGE-A4 expression
ctDNA reductions observed even at low MAGE-A4 expression
OXFORDSHIRE, UK & CONSHOHOCKEN, PA & ROCKVILLE, MD, USA I December 08, 2022 I Immunocore Holdings plc (Nasdaq: IMCR), a commercial-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, autoimmune and infectious diseases, today presented data for IMC-C103C, a bispecific T cell engager targeting MAGE-A4, in patients with ovarian cancer.
The Phase 1 data, presented in a poster at the ESMO Immuno-Oncology 2022 Congress, include 33 heavily pre-treated patients with ovarian cancer, who received doses of ≥ 90 mcg intravenously. This includes 16 new patients, and 17 patients previously reported at the ESMO Immuno-Oncology 2021 Congress, now with longer follow-up. All patients had platinum relapsed/refractory ovarian cancer (70% PARP inhibitors experienced) and were enrolled regardless of MAGE-A4 protein expression, which was analyzed retrospectively.
Of the 33 patients, 39% (13/33) were MAGE-A4 negative as measured by immunohistochemistry (IHC), and 2 patients had an unknown H score. Of the 55% (18/33) MAGE-A4 positive patients, the majority had low expression (median score = 29 of 300), and only 2 had an H score > 150.
The safety profile was consistent with that reported previously and the mechanism of action, i.e., T cell activation. No related AE led to treatment discontinuation or death.
At the time of data cut-off, 32 patients were evaluable for response, with one additional patient (H score 21) still on treatment and not having had first tumor assessment. Of the 17 evaluable MAGE-A4 positive patients, one had a durable Partial Response (PR), with a duration of 12.7 months, one patient who had a Stable Disease (SD) converted to an unconfirmed PR after the poster data cutoff date and is still ongoing, and 5 had SD. Reductions in ctDNA were observed in over half of ctDNA evaluable patients (12/22), including 7 with ≥ 50% reductions, and even in those with low or zero MAGE-A4 expression.
“Immunocore has learned from tebentafusp that OS benefit and ctDNA reduction are observed in patients with both high and low total protein expression, while RECIST responses are enriched at higher protein expression,” said David Berman, Head of Research and Development of Immunocore. “The emerging IMC-C103C results, where most patients had either no or very low MAGE-A4 expression, are consistent with the RECIST and ctDNA reduction results reported for tebentafusp.”
IMC-C103C is part of a co-development / co-promotion collaboration with Genentech, a member of the Roche Group under which Immunocore shares program costs and profits equally. Both companies are evaluating next steps for the IMC-C103C program.
About Immunocore
Immunocore is a commercial-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, autoimmune, and infectious disease. 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 TCR therapeutic, KIMMTRAK, has been approved for the treatment of HLA-A*02:01-positive adult patients with unresectable or metastatic uveal melanoma (mUM) in the United States, European Union, Canada, Australia and the United Kingdom, having demonstrated an overall survival benefit in a randomized Phase 3 clinical trial in mUM, a cancer that has historically proven to be insensitive to other immunotherapies.
SOURCE: Immunocore
Post Views: 516
