Preliminary Data of MK-1084 +/- Pembrolizumab in Solid Tumors and NSCLC

Carlos Rojas, MD, medical oncology, Centro de Investigacion Clinica, Bradford Hill, discusses preliminary findings from a phase 1 trial (NCT05067283) which evaluated MK-1084, a selective KRAS G12C inhibitor, alone in patients with advanced solid tumors, as well as in combination with pembrolizumab (Keytruda) for the first-line treatment of metastatic non–small cell lung cancer (NSCLC).

The open-label, global, dose-escalation study demonstrated that as of April 5, 2023, no dose-limiting toxicities have been reported. The overall response rate among patients in arm 1 (n = 43) was 19%, all of which were partial responses (PRs). This included 4 patients with colorectal cancer and 4 with NSCLC. In arm 2 (n = 15) the ORR was 47%, and all were PRs.

In arm 1, adverse events (AEs) of any cause were seen in 36 (84%) patients vs 13 (87%) in arm 2, but none of the AEs led to treatment discontinuation. Additionally, treatment-related AEs were seen in 22 (51%) patients in arm 1 and 11 (73%) in arm 2, but none of these AEs were grade 4 or 5.

Transcription:

0:10 | [I think that] this first report shows us that this is an active drug and safe. So now, this trial will continue with new arms, combining this with chemotherapy for example, and with other targeted therapies to try to have a strong response and a longer response, because the problem with KRAS inhibitors so far is that we're seeing response, but not as long as we would like. I think that this is the beginning of this treatment for this kind of mutation and we will try to get a more deep response that is also longer.

1:00 | We will open new arms for colorectal and for non–small cell lung cancer in the frontline in both and in colorectal also in later lines in combination with cetuximab [Erbitux]. Also, we will try another coformulation of the drug looking for a best response in patients with any tumor that harbors this mutation.

REFERENCE:

Rojas C. Safety and preliminary efficacy of the KRAS G12C Inhibitor MK-1084 in solid tumors and in combination with pembrolizumab in NSCLC. Presented at: ESMO 2023; September 29 - October 3, 2023; Madrid, Spain. Abstract 663P.