CDX-1140 Plus Pembrolizumab Elicits Responses in PD-1/PD-L1–Resistant Solid Tumors

The utilization of the anti-CD40 agonist, CDX-1140, in combination with pembrolizumab (Keytruda) was generally well tolerated and demonstrated preliminary efficacy in patients with anti–PD-1/PD-L1 resistant, locally advanced or metastatic solid tumors, according to data from an expansion cohort of the phase 1 CDX1140-01 trial (NCT03329950).

Data presented at the 2022 SITC Annual Meeting showed that of 6 evaluable patients with squamous cell carcinoma of the head and neck (SCCHN), 1 patient achieved a complete response (CR) that was ongoing at 16 months, and 1 patient experienced stable disease for 6 months. Moreover, of 5 evaluable patients with non–small cell lung cancer (NSCLC) in the expansion cohort, 4 patients experienced stable disease, lasting 13 months in one case.

“Patients enrolled in the study had progressive disease on prior anti–PD-1/PD-L1 based therapy, yet evidence of clinical benefit was observed, particularly in patients with SCCHN,” lead study author Rachel E. Sanborn, MD, medical director of the Thoracic Oncology Program and Phase I Clinical Trials Program at the Earle A. Chiles Research Institute at Providence Cancer Institute in Portland, Oregon, stated in the poster presentation of the data.

The CDX1140-01 trial evaluated CDX-1140 alone or in combination with pembrolizumab, CDX-301, or chemotherapy in patients with advanced solid tumors. Given the promising results with CDX-1140 monotherapy, investigators launched an expansion cohort in patients with SCCHN and NSCLC. Adult patients aged 18 years and older who had progression on no more than 1 prior anti–PD-1PD-/L1 regimen were evaluated.

Eligible patients were treated with 0.72 mg/kg (for the safety run-in) or 1.5 mg/kg (for the safety run-in and expansion cohort) of CDX- 1140 in combination with 200 mg of pembrolizumab once every 3 weeks. Patients who received 1.5 mg/kg of CDX-1140 were permitted to receive a dose reduction if they experienced a non–dose-limiting toxicity, including grade 2 or grade 3 treatment-related adverse effects (TRAEs), such as arthralgias, myalgias, and fatigue that interfered with a patient’s quality of life.

The primary end point of the phase 1 study was overall response rate (ORR) as determined by immune RECIST criteria.

The median duration of treatment for patients who received 1.5 mg/kg of CDX-1140 and 200 mg of pembrolizumab every 3 weeks was 2 cycles (range, 1-16).

Most patients in the expansion portion of the trial were White males. Moreover, the median age of patients with SCCHN was 61.5 years (range, 53.0-72.0) and 70.0 years (range, 60.0-78.0) for those with NSCLC. All patients had a baseline ECOG performance status of 0 or 1, and all patients in the expansion portion of the trial had received between 1 and 5 lines of prior chemotherapy or checkpoint inhibitor therapy.

In terms of safety, 1.5 mg/kg of CDX-1140 in combination with 200 mg of pembrolizumab was generally well tolerated. The most common grade 3 or higher TRAEs in patients (n= 21) were lipase increase (19%), arthralgia (14.3%), lymphocyte count decrease (14.3%), fatigue (9.5%) and aspartate aminotransferase increase (9.5%).

A total of 4 patients discontinued the study treatment because of CDX-1140 related toxicity, including grade 2 arthralgia (n = 2), grade 2 cytokine release syndrome (n = 1), grade 2 diarrhea (n = 1), and grade 3 stomatitis (n = 1).

“CDX-1140 in combination with pembrolizumab has been generally well tolerated with most drug-related AEs being grade 1 or grade 2. There were no cases of pneumonitis and no drug-related deaths,” Sanborn added.

Additionally, investigators noted expected pharmacodynamic effects in circulating immune populations, as well as soluble immune markers from patients treated with CDX-1140.

“Future studies should focus on strategies to improve the activity of CDX-1140 in combination with checkpoint blockade, which may include exploring additional combinations as well as sequencing of combination agents, particularly in patients with SCCHN,” Sanborn and colleagues concluded.

Reference

Sanborn RE, Gabrail N, Carneiro B, et al. Results from a phase 1 study of CDX-1140, a fully human anti-CD40 agonist monoclonal antibody (mAb), in combination with pembrolizumab. Presented at: 2022 SITC Annual Meeting; November 8-12, 2022; Boston, MA. Poster 596