A biologics license application seeking the approval of cosibelimab in patients with metastatic or locally advanced cutaneous squamous cell carcinoma has been accepted for filing by the FDA.
A biologics license application (BLA) seeking the approval of cosibelimab (formerly CK-301) in patients with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) has been accepted for filing by the FDA.1 The Prescription Drug User Fee Act goal date is January 3, 2024.
The BLA is based on data from a registration-enabling phase 1 trial (NCT03212404) in which the agent elicited a confirmed objective response rate (cORR) of 47.4% (95% CI, 36.0%-59.1%) based on independent central review (ICR) and by RECIST v1.1 criteria in the metastatic CSCC cohort (n = 78).2,3 In the locally advanced CSCC cohort (n = 31), cosibelimab induced a cORR of 54.8% (95% CI, 36.0%-72.7%) by ICR.4
“The filing acceptance of our BLA is a major milestone for Checkpoint and our promising cosibelimab development program,” James Olivero, president and chief executive officer of Checkpoint Therapeutics, Inc., stated in a press release. “We look forward to continuing to work closely with the FDA as we endeavor to bring cosibelimab to patients in need as quickly as possible. I would like to thank the patients and physicians who participated in the cosibelimab clinical studies, as well as our team for their hard work and dedication in achieving this important milestone.”
A high-affinity, fully human PD-L1 monoclonal antibody, cosibelimab blocks PD-L1 to reactivate T cells and has a functional fragment crystallizable region that may bind and activate natural killer cells allowing for antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity.3
The trial enrolled patients with a histologically confirmed diagnosis of metastatic CSCC that was not amenable to surgery. Patients were required to be at least 18 years of age, have an ECOG performance status of 0 or 1, and a life expectancy of at least 3 months. Those who previously received an immune checkpoint inhibitor or who had active, suspected, or documented history of autoimmune disease, were excluded. Other exclusion criteria included those who received concurrent immunosuppressive doses of steroids.
Participants were administered cosibelimab at 800 mg intravenously every 2 weeks until confirmed complete response (CR), disease progression, intolerable toxicity, or clinical deterioration followed by posttreatment follow-up.
ICR-assessed ORR according to RECIST v1.1 criteria served as the primary end point of the trial. Secondary end points comprised duration of response (DOR) for those with CR or partial response (PR), incidence and severity of treatment-emergent toxicities, and other clinical laboratory data.
In January 2022, it was announced that the metastatic CSCC cohort met its primary end point.2 Data from this cohort were subsequently shared at the 2022 ASCO Annual Meeting.3 In this cohort, the median age was 71.6 years (range, 37-91), with 71.8% of patients aged 65 years or older. Most patients were male (75.6%), White (88.5%), not Hispanic or Latino (93.6%), from Australia/New Zealand (57.7%), and had an ECOG performance status of 1 (70.5%).
The primary disease site was in the head/neck (59.0%), extremity (24.4%), trunk (11.5%), or other (5.1%). Moreover, 66.7% of patients had distant metastatic disease and the remainder had nodal disease. Regarding prior cancer-related treatment, 65.4% had radiotherapy and 9.0% had systemic therapy.
At a data cutoff date of November 18, 2021, robust and durable reductions in target lesions were reported. The median duration of follow-up was 15.2 months (95% CI, 12.0-20.5). Of those who responded to cosibelimab, 7.7% achieved a CR, 39.7% had a PR, and 15.4% had stable disease; 26.9% of patients experienced disease progression.
Response was ongoing in most patients (75.7%), with a median DOR that had not yet been reached (range, 1.4-31.8). The Kaplan Meier–estimated 6-month DOR probability rate was 88.1% (95% CI, 71.3%-95.4%); the 24-month DOR probability rate was 72.5% (95% CI, 51.6%-85.5%).
Regarding safety, 70.5% of patients experienced treatment-related adverse effects (TRAEs), with 9.0% of patients having at least 1 TRAE that was grade 3 or higher in severity. No grade 4 or 5 TRAEs were observed. Treatment-related serious AEs were reported in 3.8% of patients. One patient discontinued treatment with the agent due to pemphigoid which was determined to potentially be related to cosibelimab.
Three patients experienced AEs that resulted in death; 2 of these patients had COVID-19 and the third patient had cardiac arrest. None of these AEs were determined to be associated with study treatment.
Positive interim results from the locally advanced CSCC cohort were also released in June 2022.4 At the March 2022 data cutoff, cosibelimab induced an ORR that was noted to substantially exceed a clinically meaningful lower bound of the 95% two-sided confidence interval of 25%.
“According to US prescription claims data, in 2021, approximately 11,000 CSCC patients were treated with systemic therapies. As PD-1 inhibitors comprised less than half of patient prescriptions, CSCC remains a disease with a high need for effective and tolerable treatment options, particularly for the significant number of CSCC patients with immunosuppressive conditions or autoimmune diseases,” Olivero added in the press release. “With its unique mechanism of action and compelling safety profile, we believe cosibelimab, if approved, would be uniquely positioned to provide an important new treatment option for CSCC patients that are currently underserved by available therapies.”
In the BLA filing acceptance letter, the FDA indicated that no filing review issues had been identified and there are no plans for an advisory committee meeting to discuss the application.