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ESMO 2022 | Phase I dose escalation of IMC-F106C, a PRAME × CD3 ImmTAC bispecific protein in solid tumors

Omid Hamid, MD, The Angeles Clinic and Research Institute, Santa Monica, CA, shares the results from Phase I (NCT04262466) dose escalation of IMC-F106C, the first PRAME × CD3 ImmTAC bispecific protein in solid tumors. ImmTAC IMC-F106C consists of a T-cell receptor and CD3 engager, designed for the treatment of advanced cancers that are positive for Preferentially Expressed Antigen in Melanoma (PRAME). The Phase I trial included patients with uveal melanoma, cutaneous melanoma, ovarian cancer and lung cancer. Primary endpoints included safety and recommended dose and secondary/exploratory endpoints included efficacy, biomarkers and ctDNA response. Significant response rates in uveal melanoma, ovarian cancer and cutaneous melanoma and decreases in ctDNA levels in patients with non-small cell lung cancer was observed, although without formal response. This interview took place at the European Society for Medical Oncology (ESMO) 2022 Congress in Paris, France.

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Transcript (edited for clarity)

IMCF106C is a ImmTAC. That’s a molecule, that’s a T-cell receptor on one side and a CD3 engager on the other. The T-cell receptor engages peptides from PRAME protein that are digested and presented by tumor cells. On the other side, the CD3 engager brings the T-cell close. This is proof of principle to show efficacy of this drug in a Phase I setting for patients with cutaneous melanoma uveal, ovarian cancer, lung cancer, endometrial cancer...

IMCF106C is a ImmTAC. That’s a molecule, that’s a T-cell receptor on one side and a CD3 engager on the other. The T-cell receptor engages peptides from PRAME protein that are digested and presented by tumor cells. On the other side, the CD3 engager brings the T-cell close. This is proof of principle to show efficacy of this drug in a Phase I setting for patients with cutaneous melanoma uveal, ovarian cancer, lung cancer, endometrial cancer. So, high PRAME-expressing cancers. And of course, it was a Phase I, so safety and efficacy was important.

The safety is great. No significant toxicities. All of the cytokine release syndromes, were 1 and 2, very well tolerated. No real toxicities. No one was discontinued for toxicities, no grade 5 toxicities. Then the efficacy portion is important because this platform has been validated by a similar drug that’s been approved by the FDA for ocular melanoma, tebentafusp, which targets gp100, this targets PRANE. So the efficacy here, we saw early responses in patients. In the efficacy population, 31 patients. We saw significant response rates in uveal melanoma, ovarian cancer, and cutaneous melanoma.

We saw interesting decrements in correlatives of response, like ctDNA decreases in patients, including non-small cell lung cancer that didn’t have a formal response but had greater than 50% decrease in circulating tumor DNA. Interestingly, 80% of those patients that had ctDNA that was followed, so 20 patients, 80% of them had some decrement and a quarter of them cleared their ctDNA. So an interesting beginning to this drug. It shows a T-cell targeted therapy that’s off the shelf, a valuable and utilizable for a whole host of solid tumor types, whole host of patients age, performance status, et cetera. And as we expand, we have expansion cohorts in multiple tumor types, and we’re moving this into combinations with chemotherapy and checkpoint inhibitors. So stay tuned for more on this interesting drug.

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