Updated interim results from an open-label, multi-cohort Phase I clinical trial show patients with advanced cancers, including a registration-enabling cohort with metastatic cutaneous squamous cell carcinoma (cSCC), had significantly improved response rates to the anti-PD-L1 antibody cosibelimab.
According to researchers, patients given cosibelimab in the study had a 51.4 percent objective response rate (ORR) and a complete response rate of 13.5 percent, which itself was nearly double the number in a previous analysis. The new results from the ongoing cosibelimab trial were presented at the ESMO Virtual Congress 2020. The final results are anticipated in the summer of 2021, which study investigators believe will demonstrate that cosibelimab is capable of outperforming the two currently available immune-based therapies for metastatic cSCC while also being a safe and cheaper treatment option.
Formerly known as CK-301, cosibelimab is a fully human antagonistic monoclonal antibody that binds to the immune checkpoint PD-L1, blocking interaction with the programmed death-1 (PD-1) receptor and B7-1 receptors, triggering anti-tumor immune response by removing the suppressive effects of PD-L1 on anti-tumor CD8+ T cells to restore the cytotoxic T-cell response.
If approved by the FDA, cosibelimab would be the third immunotherapy, and the first anti-PD-L1 therapy, granted approval for use in patients with metastatic cSCC. The new class of immunotherapy drugs already has added significantly to standard treatment options, e.g., surgery and/or radiation, available to this patient population, noted Jack Jacoub, MD, a medical oncologist and Medical Director of MemorialCare Cancer Institute at Orange Coast Medical Center.
"The impact has been profound-and even to go as far as 'revolutionary' with regards to these patients-when one considers the limited and often poor options they had prior to the era of effective immune-based therapies," said Jacoub. "We use these agents often in these patients. And again, relative to the treatment options we had previously, the outcomes have been very good and well-tolerated."
Advancing the Cause
The ongoing Phase I trial of cosibelimab was launched in 2017 across 28 clinical sites in Australia, New Zealand, South Africa, Poland, Russia, Ukraine, and Thailand. The cSCC cohort includes patients with nodal and/or distant metastatic disease with the primary endpoint of ORR being assessed by an independent central review using RECIST 1.1.
Patients receive cosibelimab as a fixed dose of 800 mg every 2 weeks or 1,200 mg every 3 weeks until confirmed and worsening disease progression or clinical deterioration, followed by post-treatment follow-up. As of the interim analysis from which data was presented at ESMO, 37 patients with metastatic cSCC were evaluable for efficacy by investigator assessment with at least one post-baseline tumor assessment or discontinued treatment.
In addition to the improved ORR and complete response rates of 51.4 percent (with two patients pending confirmation) and 13.5 percent (all confirmed), respectively, responses to cosibelimab were also durable, with 91.7 percent of eligible responses lasting longer than 6 months. The median duration of response has not yet been reached-with 84.2 percent of responses and ongoing-while the longest response duration had reached 24 months at the time of the analysis.
A total of 114 patients with advanced cancers had been treated with cosibelimab and were evaluable for safety at the time of analysis. The most common treatment-related adverse events (TRAE) included fatigue (n=17, 14.9%) and rash (n=16, 14.0%), with only three patients (2.6%) discontinuing treatment due to a TRAE. Grade >=3 TRAEs occurred in six patients (5.3%), most commonly anemia and fatigue (each n=2, 1.8%, grade 3 only).
Philip Clingan, a professor and medical oncologist at Southern Medical Day Care Centre in Wollongong, Australia, and co-principal investigator of the cosibelimab study, said the interim data confirms safety and efficacy results previously seen in patients with metastatic cSCC treated with the immunotherapy (Ann Oncol 2019; doi.org/10.1093/annonc/mdz244.031).
"Cosibelimab's well-tolerated safety profile and early achievement of complete responses seen to date have provided a real benefit to our patients," Clingan said in presenting the data at ESMO. "We look forward to the full cohort results next year and advancing this important treatment option forward."
Joining the Fight
A type of nonmelanoma skin cancer, cSCC is the second most frequently diagnosed cancer in North America. It is excluded from national cancer registries, however, so the precise incidence of metastases and death is unclear (J Am Acad Dermatol 2013; doi: 10.1016/j.jaad.2012.11.037). One large study estimated 1.2 million people in the U.S. were diagnosed with cSCC in 2012. While most cases were localized and successfully treated with surgery and/or radiation, nearly 4 percent of patients developed nodal metastases and roughly 2 percent died (JAMA Dermatol 2013; doi:10.1001/jamadermatol.2013.2139).
Earlier this year, the FDA approved pembrolizumab for patients with recurrent or metastatic cSCC not curable by surgery or radiation. Efficacy of the immunotherapy was investigated in KEYNOTE-629 (NCT03284424), a multicenter, multi-cohort, non-randomized, open-label clinical trial. The reported ORR was 34 percent (95% CI: 24, 44) and median response duration was not reached (range: 2.7, 13.1+ months). The recommended doses for cSCC are 200 mg every 3 weeks or 400 mg every 6 weeks.
FDA approval of pembrolizumab followed the 2018 nod to another anti-PD-1 antibody called cemiplimab-rwlc. Phase I and Phase II studies of cemiplimab-rwlc included patients with locally advanced and metastatic cSCC. In the Phase II study, 59 patients with metastatic disease were treated with 3 mg/kg or a single dose of 350 mg. The ORR was 47.5 percent and the disease control rate was 61 percent, with 6.8 percent of patients achieving complete response (Drugs Context 2019; doi:10.7573/dic.212583).
By comparison, the complete response rate of patients treated in the cosibelimab study and included in the results reported at ESMO was threefold higher than the rate demonstrated by pembrolizumab, which study investigators say highlights a half-life that supports sustained tumor-target occupancy greater than 99 percent, and a functional Fc domain capable of inducing antibody-dependent, cell-mediated cytotoxicity.
Chuck Holt is a contributing writer.