Nicholas Coupe, MBBS, PhD, Provides Update on Phase 2 Study of IMM60 in Advanced Melanoma/NSCLC

An initial readout of an ongoing phase 1/2 study (ISRCTN80472712) from the 2022 American Society of Clinical Oncology Annual Meeting indicated that treatment with IMM60 in patients with advanced melanoma and non–small cell lung cancer (NSCLC) yielded promising preliminary safety data, according to lead author Nick Coupe, MBBS, PhD.

Aside from reporting that no adverse effects occurred in the 5 patients who were treated, Coupe, a consultant medical oncologist at Churchill Hospital, highlighted a notable reduction in tumor volume for 1 patient and a mixed response in another. Although the work is early, he explained how the research may lay the groundwork for further research.

“The hope is that we demonstrate yet another way of enhancing antitumor immune responses,” Coupe explained. “There is obviously a lot of work in this field, [including] a lot of existing work looking at new targets. This is quite a novel approach. It’s not targeting a specific checkpoint; it’s targeting a component of the immune system that has a broad effect. It is quite a novel approach. By doing so, hopefully we can complement existing therapies with PD-1 [inhibitors]. There may be rationale to combine this with other treatments. Hopefully, it does lead to some excitement and yet another element of immunotherapy research in a clinical setting.”

In an interview with CancerNetwork^®, Coupe highlighted the mechanism of action of the novel synthetically derived agonist of invariant natural killer cells formulated in the PORT-2 liposome and what future research efforts might look like.

CancerNetwork^®: Could you start off by telling me about the rationale for this study?

Coupe: The rationale stems from an unmet need in both tumor groups. We we’re looking at patients with metastatic melanoma and non–small cell lung cancer. It’s well known that there have been some big advances, particularly in the field of melanoma, in recent years. Despite that, close to 50% of patients with metastatic disease will eventually succumb. For those patients who require optimal treatments, combination immunotherapy has [a roughly] 60% grade 3 toxicity rate; it’s quite a toxic treatment.

In lung cancer, immunotherapy has been a big step forward with PD-1 inhibition, but in this group, the outcomes are still very poor, with only around 20% to 30% of people experiencing long-term survival. There’s a big unmet need, and the rationale for this study stems from some preclinical work that goes back a number of years. IMM60 is a molecule that was discovered Oxford. It has a broad impact upon the immune system targeting various components. The hope is that it can synergize with the therapies that are already in existence so that we may capitalize on the gains that are already made.

What is the mechanism of action of IMM60?

It’s an invariant, natural Killer T-cell agonist. Natural killer T cells are a subset of the T-cell population in the body. [They aren’t] as well studied as other subsidiaries, but they basically carry a very important function that affects multiple arms of the immune system. It has been known for some time that patients with high levels of invariant natural kill T-cell activation have more favorable cancer outcomes. PORT-2 is an activator of this population. It has direct impact against tumors in terms of upregulating PD-L1 expression, which we know is favorable because it can enhance the effectiveness of existing therapies. It is also a potent activator of not just natural killer cells, but also antigen-progenitor cells and CD8 T cells, which are the effector cells that drive antitumor responses. There is also some evidence that it helps create a favorable tumor microenvironment, potentially overcoming some of the resistance mechanisms that [lead to certain patients failing to derive] benefit from existing therapies.

At this year’s meeting, what findings read out from this study?

[Data were read-out from] two-thirds of the phase 1 study population, so it is very much in the in the early phases of development. We’re still in the dose-escalation phase. We presented the results of 5 patients who have been treated so far for dose level 3 and dose level 1, and 2 patients were in the in the second dose level. What we have seen so far for the 5 patients treated was 1 mixed response with the second dose and there was a quite impressive tumor reduction in a number of sites. In this particular case, as I just referenced, a mediastinum mass [went] from 4 cm down to 1.9 cm in a patient who was heavily pretreated with all existing standard therapies for melanoma. We also saw from a toxicity point of view that the treatment was safe. It only caused a very low number of grade 1 or grade 2 toxicities, so it’s very well tolerated. We’ve seen no SAEs [serious adverse effects] or AEs requiring any specific intervention.

Where do you see future efforts being focused here?

We aim to complete the dose-escalation study soon. We’re recruiting and hope to follow patients at their current dose level. Once we complete the dose-escalation phase, we’ll start our safety phase where we will be giving IMM60 PORT-2 alongside pembrolizumab [Keytruda]. Once we’ve completed the safety cohort, the next phase is to move into a phase 2 study. In this part of the study, we’re going to recruit over 80 patients from a number of different sites where we’ll be comparing a combination of PORT-2 and pembrolizumab vs pembrolizumab alone in patients with advanced melanoma and [NSCLC who] have not been pretreated.

Reference

Coupe N, Walters IB, Kramer RA, et al. A phase 1 first-in-human dose finding/randomized phase 2 study of IMM60 and pembrolizumab (PEM) in advanced melanoma and non–small cell lung cancer (NSCLC; IMP-MEL). J Clin Oncol. 2022;40(suppl 16):2582. doi:10.1200/JCO.2022.40.16_suppl.2582