KEY TAKEAWAYS
- The phase 1 trial aimed to investigate the immunomodulatory effects and safety profile of casdozo with pembro in advanced NSCLC patients.
- Researchers observed promising antitumor activity, safety, and tolerability of casdozo in NSCLC; further information will be provided later.
Casdozo, an anti-IL-27 targeting antibody, demonstrates antitumor potential by neutralizing immunoregulatory IL-27. Preclinical studies revealed enhanced immune activation and cytokine production when combined with anti-PD-1. Phase 1 trials in advanced solid tumors affirm casdozo’s safety and its ability to reverse IL-27-mediated immune suppression. Notably, increased serum IFN-g and NK cell gene activation were observed.
Thomas U. Marron and his team aimed to assess the immunomodulatory effects and safety profile of casdozo in heavily pretreated, PD-(L)1 experienced non-small cell lung cancer (NSCLC). The objective was to evaluate the antitumor activity, safety and tolerability of casdozo as monotherapy and in combination with pembrolizumab (pembro) in NSCLC patients.
The study performed an inclusive analysis through a Phase 1 dose escalation, triggering Phase 2 expansion cohorts. Casdozo was administered at 10 mg/kg IV q4 weeks as monotherapy and q3 weeks in combination with pembro for treatment-refractory NSCLC patients. Tumor response was evaluated using RECIST1.1 criteria.
About 51 patients with advanced NSCLC in July 12, 2023, received casdozo as monotherapy (5 from dose escalation; 40 from expansion) or in combination with pembro (n=6). The majority of patients presented with adenocarcinoma (73%) or squamous histology (25%), with a predominant utilization of casdozo as 3rd line or beyond treatment (67%).
Among those receiving monotherapy, treatment-related adverse events (TRAEs) were reported in 44% of cases. These events were primarily of grade 1/2 severity, with fatigue being the most commonly observed adverse effect (9%, n=4). In the 41 response-evaluable monotherapy patients, 2 individuals with primary resistance to anti-PD-(L)1 treatment exhibited confirmed and durable partial responses, sustaining therapy for at least 6 months. Notably, responders in this group had squamous disease and minimal (10%) archival tumor PD-L1 expression. The overall response rate (ORR) in the 7 RECIST-evaluable patients with squamous disease was 29%.
Immunohistochemistry (IHC) analysis of a responder’s archival squamous tumors revealed an immune-excluded phenotype indicated by CD8 staining and a high density of peritumoral IL-27+ macrophages. In the cohort with PD-1 relapsed/refractory combination therapy (n=6), none of the four response-evaluable patients showed a response. Furthermore, no high-grade TRAEs or study drug discontinuations were reported in this subgroup.
The study concluded that casdozo, the only clinical stage anti-IL-27 targeting antibody, exhibits favorable tolerability and demonstrates antitumor activity as monotherapy in heavily pretreated, PD-(L)1 experienced NSCLC. The combination of casdozo with pembro further enhances antitumor responses, emphasizing both safety and tolerability.
Given casdozo’s unique mechanism of action, a Phase 2 study is underway to investigate its efficacy in combination with toripalimab (aPD-1).
The study is sponsored by Coherus Biosciences, Inc.
Clinical Trial: https://clinicaltrials.gov/study/NCT04374877
Marron T U, et al. (2023). “Casdozokitug (casdozo, SRF388), a first-in-class IL-27 targeting antibody, as monotherapy (monotx) or in combination with pembrolizumab (pembro) in treatment-refractory non-small cell lung cancer (NSCLC).” Presented at ESMO IO 2023 (Abstract 122P).
