Nicholas Coupe, MBBS, PhD, oncologist, Oxford University Hospitals, NHS Foundation Trust, discusses the rationale for investigating IMM60 with pembrolizumab (Keytruda) in patients with advanced melanoma or metastatic non-small cell lung cancer (NSCLC), as well as key background information that led to this investigation.

At the 2023 ASCO Annual Meeting, investigators presented data from the ongoing, first-in-human, dose-finding, randomized phase 1/2 IMPORT-201 trial (NCT05709821) which is investigating the novel agent IMM60 as both a monotherapy and in combination with the PD-1 inhibitor pembrolizumab.

The invariant natural killer (NK) T-cell agonist IMM60 is a unique therapy, Coupe begins. Invariant NK T cells are cells that have a broad range of activity across the immune system, affecting both the adaptive and innate arms of the immune system, he says. Once activated, invariant NK T cells can directly affect tumors, Coupe notes. Notably, there is some preclinical work showing that NK T cells can directly upregulate PD-L1 expression in tumor cells, Coupe says, explaining that they can also engage favorably with antigen-presenting cells, such as dendritic cells, which can potentially enhance their immunogenic effect against tumor cells.

Additionally, NK T cells can increase the ability of cytotoxic T cells to be recruited to attack tumor cells and can alsoengage with B-cells, potentially affecting the way the antibodies engage with the tumors, Coupe expands. Moreover, research shows that invariant NK T cells play a key role in optimizing the tumor microenvironment, making it a favorable environment for the destruction of tumor cells. Other research with NK T cell agonists has been conducted in the past, and a preceding compound has demonstrated some activity in this setting, Coupe says. However, the pharmacokinetic and pharmacodynamic profiles of IMM60 supersede that activity, and in the future, IMPORT-201 investigators hope to show promising clinical activity with this agent, Coupe concludes.

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Nicholas Coupe, MBBS, PhD, discusses the rationale for investigating IMM60 with pembrolizumab in patients with advanced melanoma or metastatic non-small cell lung cancer, as well as key background information that led to this investigation. 


Dr Coupe on the Background of IMM60 With Pembrolizumab in Melanoma or NSCLC

Nicholas Coupe, MBBS, PhD, oncologist, Oxford University Hospitals, NHS Foundation Trust, discusses the investigation of IMM60 plus pembrolizumab (Keytruda) in patients with advanced melanoma or metastatic non-small cell lung cancer (NSCLC).

The phase 1/2 IMPORT-201 trial (NCT05709821) is investigating IMM60 monotherapy and in combination with pembrolizumab. Data from the phase 1 portion of the trial presented at the 2023 ASCO Annual Meeting showed that IMM60 was well-tolerated at doses of 1 mg/mg2, 3 mg/mg2, and 9 mg/mg2, although only 12 patients have been treated with the single agent or combination thus far in the first-in-human study, Coupe begins. Only a small number of grade 1/2 toxicities have been reported, and no grade 3 or higher adverse effects have occurred, he says. in patients. Notably, there was not a significant increase in toxicity at increased dose levels, and expansion to additional dose levels is possible, Coupe explains.

Pharmacokinetic data demonstrated that IMM60 reached appropriate concentrations in the blood, he expands. In patients treated with IMM60 alone, tumor reduction has been observed at several sites in a heavily pretreated patient population, Coupe says, noting that there are patients who had exhausted other standard-of-care treatment options.

Moreover, one patient treated with the combination of IMM60 and pembrolizumab experienced a 100% reduction in target lesion in the liver, Coupe continues. This response was observed after 3 months of treatment; however, it is too early to know if that response could be attributed to pembrolizumab or IMM60, and further study and follow-up could help provide additional data regarding the combination, Coupe concludes.

Nicholas Coupe, MBBS, PhD, discusses the investigation of IMM60 plus pembrolizumab in patients with advanced melanoma or metastatic non-small cell lung cancer.


Nicholas Coupe, MBBS, PhD

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Dr Coupe on the Background of IMM60 With Pembrolizumab in Melanoma or NSCLC

Dr Coupe on the Investigation of IMM60 Plus Pembrolizumab in Advanced Melanoma and NSCLC