Combination therapy with low-dose ipilimumab with pembrolizumab demonstrates significant antitumor activity in patients with melanoma following disease progression on a PD1 antibody, according to results from a phase 2 study presented at the virtual 2020 ASCO Annual Meeting.

“At its base our study examines pembrolizumab… and ipilimumab.. in patients refractory to a first-line PD1 antibody,” explained Daniel Olson, MD, University of Chicago Comprehensive Cancer Center, Illinois, during his presentation.

“Observations that combined checkpoint therapy provides a likely higher clinical benefit and that low-dose ipilimumab may make the regimen more tolerable provided the basis for our own trial,” he continued.

The trial enrolled patients with advanced melanoma who received no prior CTLA4 antibody for metastatic disease and had progressed on immediate prior treatment with a PD1 antibody. Patients received pembrolizumab 200 mg IV every 3 weeks plus ipilimumab 1 mg/kg every 3 weeks for 4 doses. Pembrolizumab was continued alone for up to 2 years.

The primary end point of the trial was response rate per irRECIST criteria. Secondary end points included safety, progression-free survival (PFS), and overall survival (OS).

As reported in 2018, the trial met its primary end point after 35 patients with 10 of 22 evaluable patients achieving a response. The trial was expanded to enroll a total of 70 patients. Data analysis cutoff was January 30, 2020.

Of the 70 patients enrolled in the trial, 67 were evaluable for treatment response. The median length of treatment of a prior PD1 antibody was 4.8 months.

The response rate among evaluable patients was 31% with 21 of 67 patients achieving a response. Overall, 4 patients achieved a complete response (CR), 17 achieved a partial response (PR), and 16 achieved stable disease (SD). The irRECIST response rate among evaluable patients was 27% (17 of 67 patients achieving a response) because 4 patients with a PR and 6 patients with SD had unconfirmed responses.

Additionally, median PFS was 5.0 months (95% CI, 2.8-8.3) and median OS was 24.7 months (95% CI, 15.2-undetermined). Grade 3-4 treatment-related adverse events were reported in 15 (27%) of 70 patients enrolled on the study, the most common being diarrhea, rash and transaminase elevation.

“In summary, this is the largest prospective study of a PD1 antibody plus CTLA4 antibody demonstrating antitumor activity and tolerability in melanoma post-progression on a prior PD1 antibody,” concluded Dr Olson.—Janelle Bradley

Olson D, Luke JJ, Poklepovic AS, et al. Significant antitumor activity for low-dose ipilimumab (IPI) with pembrolizumab (PEMBRO) immediately following progression on PD1 Ab in melanoma (MEL) in a phase II trial. Presented at: the 2020 ASCO Annual Meeting; May 29-31, 2020. Abstract 10004.