Cosibelimab Elicits Early Activity in NSCLC and Cutaneous Squamous Cell Carcinoma


November 12, 2020 - The investigational PD-L1 inhibitor cosibelimab demonstrated durable and robust responses in patients with non–small cell lung cancer and cutaneous squamous cell carcinoma.

The investigational PD-L1 inhibitor cosibelimab demonstrated durable and robust responses in patients with non–small cell lung cancer (NSCLC) and cutaneous squamous cell carcinoma (cSCC), according to interim phase 1 results of Study CK-301-101 (NCT03212404) that were presented during the virtual 2020 SITC Annual Meeting.1

Results showed that in the cohort of patients with NSCLC, the objective response rate (ORR) was 44.0% (95% CI, 24.4%-65.1%), the investigators wrote in a poster that was presented during the meeting. The median duration of response (DOR) and progression-free survival (PFS) was 15.3 months (95% CI, 11.0-19.6) and 10.3 months (95% CI, 7.0-13.7), respectively.

In patients with locally advanced or metastatic cSCC, the agent led to a 51.1% ORR (95% CI, 95% CI, 36.1%-66.0%), which included 5 complete responses and 19 partial responses (PRs)—12 of which were confirmed. Eighty-three percent of responses were still ongoing, and the median DOR and PFS were not yet reached. These data were presented previously at the virtual 2020 ESMO Congress.2

“The single-agent activity of cosibelimab in NSCLC is compelling, with the observed 44.0% objective response rate and 10.3-month median progression-free survival comparing favorably to the datasets generated in similar subjects from the PD-(L)1 therapies available today,” said James F. Oliviero, president and chief executive officer of Checkpoint Therapeutics, Inc., the developer of cosibelimab.3 “Based on the strength of these results, we intend to initiate a phase 3 registration-enabling trial evaluating cosibelimab in combination with chemotherapy in first-line, metastatic NSCLC patients.”

In the ongoing, international, multicenter, multicohort trial, investigators evaluated cosibelimab in patients with select advanced cancers, which included previously untreated PD-L1–high NSCLC and locally advanced or metastatic cutaneous squamous cell carcinoma.

To be eligible for enrollment, patients must have had an ECOG performance status of 0 or 1. In the NSCLC cohort, patients must have stage IV disease with PD-L1 expression with a tumor proportion score of at least 50%, and cannot have received prior treatment for advanced or metastatic disease; those with EGFR/ALKabnormalities are not permitted.

In the cSCC cohort, patients must have had unresectable locally advanced or metastatic cSCC that is not amenable to local therapy.

Additionally, patients who received prior immune checkpoint inhibitors, have active or suspected autoimmune disease, and immunosuppressive doses of steroids are not eligible for enrollment.

Patients received a fixed dose of cosibelimab at 800 mg every 2 weeks or 1200 mg every 3 weeks until confirmed and worsening disease progression, or clinical deterioration, followed by posttreatment follow-up. Disease was assessed via investigators through RECIST 1.1 criteria and follow-ups were conducted every 8 weeks for the first 32 weeks on study, followed by every 12 weeks.

The primary end point is efficacy via ORR and safety and tolerability in the NSCLC and cSCC cohorts; secondary endpoints include DOR and PFS.

As of October 9, 2020, there were 25 patients in the NSCLC cohort and 58 in the cSCC cohort who had been enrolled and treated with the investigative agent.

In the NSCLC cohort, the median age was 64 years (range, 29-78), and 11 patients (44.0%) were at least 65 years old. Eighteen patients (72%) were male; 7 patients (28.0%) and 18 patients (72.0%) had ECOG performance statuses of 0 and 1, respectively. All patients had metastatic disease at screening, and 3 patients (12.0%) received prior radiation.

In the cSCC cohort, the median age is 71 years (95% CI, 42-95), and 42 patients (72.4%) of those were 65 years or older; 43 patients (74.1%) were male. Thirteen patients (22.4%) had an ECOG performance status of 0 and 45 (77.6%) had a score of 1. A total 84.5% of patients in this cohort had metastatic disease, 36 (62.1%) had received prior radiation, and 6 patients (10.3%) had received prior systemic therapy.

As of the data cutoff, 25 patients with NSCLC and 47 with cSCC were evaluable for response. In the cSCC, 41 of these patients had metastatic disease versus 6 who had locally advanced cSCC. 

Additional results in the NSCLC cohort showed that the 44.0% ORR comprised of all PRs; the stable disease (SD) rate was 32% and 8% of patients experienced progressive disease (PD). Four patients were not evaluated, and 4 (36.4%) had responses ongoing.

In those with cSCC, the SD and PD rates were 17.0% and 23.4%; 4 patients were not evaluated. In metastatic patients, the ORR was 51.2% versus 50.0% in those with locally advanced disease. Moreover, deep reductions in target lesions were observed, with 14.9% (n = 7) of patients experiencing a CR in target lesions.

Regarding safety, cosibelimab was found to have a predictable and manageable safety profile. The most common treatment-related adverse events (TRAEs) included fatigue (15.4%), and rash (13.8%); 2 patients had grade 2 pneumonitis. There were also no reported cases of colitis or hepatitis. Grade 3 or higher TRAEs occurred in 4.9% (n = 6) patients, and ones that were observed in more than 1 patient included anemia and fatigue (n = 2 each) and were both grade 3.

A registration-enabling trial is ongoing in patients with locally advanced or metastatic cSCC that is evaluating the efficacy and safety of cosibelimab at the 800-mg dose every 2 weeks, as well as the 1200-mg dose on an every-3-week regimen.

“The annual market for PD-(L)1 therapies in NSCLC is approximately $10 billion and growing,” Oliviero concluded. “If approved, we believe cosibelimab could capture meaningful market share as a lower-priced alternative to therapies currently available, and NSCLC is an ideal follow-on to our planned first indication of cutaneous squamous cell carcinoma, for which topline results from an on-going registration-enabling trial are expected in the second half of 2021.”


  1. Harris DL, Brungs D, Ladwa R, et al. Cosibelimab, an anti-PD-L1 antibody: preliminary safety and efficacy results from a global, multicohort phase 1 clinical trial. Presented at: 2020 SITC Annual Meeting; November 10-15; 2020; virtual. Abstract 399.
  2. Clingan PR, Brungs D, Ladwa R, et al. Cosibelimab, an anti-PD-L1 antibody in metastatic cutaneous squamous cell carcinoma (CSCC): preliminary safety and efficacy results from a phase 1 clinical trial. Presented at: 2020 ESMO Congress; September 19-21, 2020; virtual. Abstract 1084P.
  3. Checkpoint Therapeutics announces presentation of updated cosibelimab lung cancer results at the Society for Immunotherapy of Cancer (SITC) 35th Anniversary Annual Meeting. News release. Checkpoint Therapeutics. November 9, 2020. Accessed November 12, 2020.
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