Omid Hamid, MD, on Cutaneous Melanoma: Update on a Bispecific Protein Under Study

2024 ASCO Annual Meeting


Omid Hamid, MD, of The Angeles Clinic and Research Institute, a Cedars-Sinai affiliate, discusses updated data on IMC-F106C, a novel bispecific protein that, in a phase I safety and efficacy study, exhibited clinical activity in patients with unresectable or metastatic cutaneous melanoma who were pretreated with immune checkpoint inhibitors. A phase III trial of IMC-F106C with nivolumab in the first-line setting of metastatic disease has been initiated (NCT06112314; Abstract 9507).


Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Today I am going to talk about IMC-F106C, which is an ImmTAC now called brenetafusp and this is made by Immunocore. We're all familiar with ImmTACs, immune-mobilizing T-cell receptors against cancer. It's a bispecific that targets CD3 on one side and a tumor produced protein on the other. This one targets PRAME, proteins of PRAME. This is an update of the data that I presented at ESMO 2022 about this ImmTAC that targets PRAME. In 2022 we talked about all solid tumors. This update is in cutaneous melanoma. 47 patients with single agent brenetafusp and then a nine patient combination with pembrolizumab looking at safety and efficacy. We know that ImmTACs work. This was proven with tebentafusp in uveal melanoma. We know that ImmTACs can be combined with anti-PD-1, PD-L1 and anti-CTLA-4. We did that in cutaneous melanoma and published it in JTSI. This shows a updated expansion in escalation cohorts in cutaneous melanoma. And what we saw was very interesting. We saw response, of course. There is a clinical benefit of about 50%. There is a response rate of 11% and then stable disease or better, a little shrinkage from stable diseases there. What we found is this drug, the clear benefit comes in stable disease or better. It's not just an overall response with this mechanism. We also found that the responses were durable. In those patients that had stable disease, minimal reduction or better, they had a long-term durable benefit. We saw this benefit in patients who were PRAME positive, which gives credence to the mechanism that this ImmTAC is targeting PRAME. We saw it in BRAF mutant patients. We saw it in heavy tumor burden patients and we saw it in patients with melanoma that have brain and liver metastases or both. And this is what we're looking for. This cohort of patients were heavily pretreated. They had had at least two PD-1 containing regimens. 80% had seen anti-CTLA-4 and four fifths of those had seen anti-CTLA-4 and PD-1 together. And about 38% had seen another immuno-oncology compound on top of that, which is why this is so interesting. Toxicity was tolerable, mainly grade one two cytokine release syndrome. And what we saw was it was tolerable when combined anti-PD-1 therapy. There were nine patients, six of them were primary resistant. And what we saw there is molecular response and a 1PR. And that was held throughout in the combination cohorts of brenetafusp and anti PD-1 with pembrolizumab in other solid tumors. Other solid tumors we saw that tolerability. Why is this important? Well, this is another tool in our toolkit against melanoma. Why else is it important? Melanoma sets the standard for other solid tumors. We've seen responses in other solid tumors as I presented endometrial, ovarian, uveal. And we're looking at it in lung cancer and that's interesting. What we also found is that there is a T-cell signature that indicates better response. Naive and STEM central memory T-cells, when those were higher, those patients were the ones that benefited the most. And that was found in earlier lines of therapy. We are now accruing to a major phase three trial of brenetafusp and nivolumab versus nivolumab alone or nivolumab and ipilimumab in the first line. And this will show the benefit of this drug in cutaneous melanoma. I look forward to accruing to that study. I look forward to understanding the mechanism of action of this class of drugs. I have no doubt that when we present more data on the T-cell fitness signature and in other cohorts upcoming meetings, that you'll be as excited about this platform and about this drug, brenetafusp, as I am.

Related Videos

Gastroesophageal Cancer

Jens Marquardt, MD, and Jens Hoeppner, MD, on Esophageal Cancer: Phase III Findings on Chemotherapy vs Chemoradiation

Jens Marquardt, MD, of the University of Lübeck, and Jens Hoeppner, MD, of the University of Bielefeld, discuss findings from the ESOPEC trial, which showed that perioperative chemotherapy (fluorouracii, leucovorin, oxaliplatin, docetaxel) and surgery improves survival in patients with resectable esophageal adenocarcinoma when compared with neoadjuvant chemoradiation (41.4 Gy plus carboplatin and paclitaxel) followed by surgery (LBA1).

Gynecologic Cancers

Jean-Marc Classe, MD, PhD, on Ovarian Cancer: New Data on Lymphadenectomy From the CARACO Trial

Jean-Marc Classe, MD, PhD, of France’s Nantes Université, discusses phase III results showing that systematic lymphadenectomy should be omitted in patients with advanced epithelial ovarian cancer with clinically negative lymph nodes, as well as those undergoing neoadjuvant chemotherapy and interval complete surgery (LBA5505).

Multiple Myeloma

Claudio Cerchione, MD, PhD, on Staging Multiple Myeloma: New Findings on FDG PET/CT Scans and Whole-Body MRI

Claudio Cerchione, MD, PhD, of Italy’s Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, discusses preliminary findings from a prospective trial suggesting that by adding whole-body MRI to fludeoxyglucose-18 (FDG) PET/CT scans, clinicians may detect bone lesions earlier and more accurately in patients with either newly diagnosed or relapsed multiple myeloma, thus translating into potentially better outcomes (Abstract 7512).

Breast Cancer

Reshma Jagsi, MD, DPhil, and Tarah J. Ballinger, MD, on Early-Stage Breast Cancer in Black Women: Docetaxel and Peripheral Neuropathy

Reshma Jagsi, MD, DPhil, of Emory University Winship Cancer Institute, and Tarah J. Ballinger, MD, of Indiana University Simon Comprehensive Cancer Center, discuss the disparate burden of taxane-induced peripheral neuropathy in Black women with early-stage breast cancer and how a tailored trial for this population showed that using docetaxel as the preferred taxane may be beneficial (LBA503).


Muhit Özcan, MD, on CLL/SLL: Report on a Still-Recruiting International Study of Nemtabrutinib, Venetoclax, and Rituximab

Muhit Özcan, MD, of Turkey’s Ankara University School of Medicine, discusses the ongoing phase III BELLWAVE-010 study of nemtabrutinib plus venetoclax vs venetoclax plus rituximab in previously treated patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) (Abstract TPS7089).