Immunotherapy for Cold Tumors: REGN7075 Effective in Early Trials


Neil Segal, MD, discussed findings from a phase 1/2 trial investigating REGN7075 in patients with solid tumors refractory to immunotherapy.

Tumor cell being attacked - Generated with Google Gemini AI

Tumor cell being attacked - Generated with Google Gemini AI

June is Cancer Immunotherapy Month, and Targeted Oncology is highlighting stories on this developing field of research.

REGN7075, a new type of immunotherapy drug, is being investigated for its ability to fight cancer. A phase 1/2 study (NCT04626635) presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting focused on the early stages testing in humans with advanced cancers who had run out of other treatment options.

The drug works by stimulating the immune system to attack cancer cells. Unlike other immunotherapies, it targets EGFR found on some tumor cells and activates T cells.

The study involved 94 patients, with the majority having microsatellite stable colorectal cancer (MSS CRC), a type historically unresponsive to immunotherapy. REGN7075 was well-tolerated with manageable adverse events. In patients with MSS CRC without liver metastases, the drug showed promising results, with a 20% response rate and an 80% disease control rate.

These results suggest REGN7075 may be effective against a cancer type typically not responsive to immunotherapy. The study is ongoing, with further testing planned in different tumor types with varying levels of EGFR.

In an interview with Targeted OncologyTM, Neil Segal, MD, PhD, medical oncologist at Memorial Sloan Kettering Cancer Center, who presented the study’s findings at ASCO, discussed the drug, the study’s goals, and next steps of research.

Neil Segal, MD, PhD

Neil Segal, MD, PhD

Targeted Oncology: What are the unmet needs in this patient population?

Segal: We have seen marked successes of immunotherapy across many different types of tumors. However, there is still an unmet need for many patients who have these cold tumors or these poorly responsive tumors to try to augment anticancer immunity further so that we can see this clinical benefit extended to more patients. For example, colorectal cancer is a cold tumor, which has been refractory to immunotherapy, historically, looking back at multiple trials. So that is the unmet need, to find better therapies for patients with colorectal cancer or cold tumors.

What is this study evaluating?

We are investigating REGN7075. The aim is to turn cold tumors hot. REGN7075 binds to EGFR in the tumor, and it binds to CD28 on the surface of the T cells, and thereby interacts with T cells that are in the tumor microenvironment. The way that this works is because tumor cells present peptides in the setting of [major histocompatibility complex (MHC)] class I to the T-cell receptor, and that provides signal 1 to the T-cell. Then REGN7075, by binding to CD28, elicits CD28. In effect, it turns the tumor cell almost into an antigen-presenting cell because antigen-presenting cells use the costimulatory pathway of CD28 to activate T cells, to enhance T-cell activation, T-cell proliferation, and use T-cell memory. The intention thereby is to augment the immune response to create antitumor effect.

Could you summarize your findings?

This was a phase 1/2 first-in-human study. The primary objective of the study was to look at safety, being a phase 1 trial. As a secondary end point, we evaluated efficacy. We completed dose escalation through 900 mg, and we reported safety in that cohort. During the course of the study, we identified that the effective doses are from 100 mg upwards. We focused on patients who received an effective dose of the therapy to report the efficacy results.

Patients were eligible if they had a tumor that is known to express EGFR,for example, colon cancer.The majority of patients enrolled in the study had microsatellite stable or mismatch repair proficient colorectal cancer, historically immunotherapy resistant. We focused on the efficacy results within that population of patients. Across all [patients with] MSS colon cancer patients treated with active doses, we saw a 6% response rate, which included 3 responding patients, 2 with a partial response, and 1 with a complete response, including some patients with deep responses.

We next looked at patients without liver metastases because it is known that the presence of liver metastases is considered a poor prognostic indicator for response to immunotherapy. We are interested in looking specifically at that population within a subgroup of MSS colorectal cancer patients who did not have liver metastases, which includes 15 patients. There were 3 responders, and we observed a response rate in this group of 20% with the disease control rate of 80%.

Did you identify any relevant safety signals?

Overall, the drug was generally tolerable. There were no [dose-limiting toxicities (DLTs)] that were identified up to 900 mg. Dose escalation is continuing.

We observed treatment-related adverse events amongst the patients, and we have reported the incidence of all related events as well as their grade 3 or 4 events. If we break it down into the toxicities that occurred in more than 5% of patients, we see a proportion of patients who developed infusion reactions, which were predominantly grade 1 or grade 2. There were a small number of grade 3 infusion reactions also noted. In general, what we observed is that these infusion-related reactions occurred during the initial infusion, so does 1 or dose 2, and they could, for the most part, be mitigated with appropriate medications as well as split or step-up dosing. Other adverse events that occurred in more than 10% of patients included acneiform skin rashes, maculopapular skin rashes, and nausea.

Are there any other next steps planned for this research?

Going forward, the aim is to involve more patients and to do further assessment. There are expansion cohorts that have opened which include patients with lung cancer, cutaneous squamous cell cancer, [and] head and neck cancer, and we are treating additional patients with MSS colorectal cancer in backfill cohorts and expansion cohorts.

Segal N, Girda E, Sohal D, et al. A phase 1/2 study of REGN7075 in combination with cemiplimab (cemi) in patients (pts) with advanced solid tumors: efficacy and safety results. J Clin Oncol. 2024; 42(suppl 16):2503. doi:10.1200/JCO.2024.42.16_suppl.2503
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