Jonathan Riess, MD, discusses data for IO102-IO103 plus pembrolizumab in advanced HSNCC and NSCLC with high PD-L1 expression.
The emergence of therapeutic cancer vaccines represents a promising evolution in immuno-oncology, aiming to extend the benefits of checkpoint inhibition to a broader patient population, according to Jonathan Riess, MD.
This concept was reflected in a phase 2 basket trial (NCT05077709) presented by Reiss and colleagues at the
In terms of efficacy, the primary end point of overall response rate (ORR) was met in patients with HNSCC (n = 18) at 44.4% (95% CI, 21.5%-69.2%). Similar activity was observed in the NSCLC cohort, where the ORR was 48.4% (95% CI, 30.2%-66.9%). The median progression-free survival (PFS) was 7.0 months (95% CI, 2.0-13.1) in the HNSCC cohort and 8.1 months (95% CI, 4.2-17.7) in the NSCLC group, with 18-month PFS rates of 22% (95% CI, 7%-43%) and 31% (95% 16%-48%), respectively. Median overall survival (OS) was 22.3 months (95% CI, 9.4-not evaluable [NE]) in patients with HNSCC and 22.6 months (95% CI, 16.6-NE) in those with NSCLC, with corresponding 18-month OS rates of 61% and 64%, respectively.
“[The study] showed [that the combination was] safe and tolerable. Toxicity was in line with what you’d expect with single-agent pembrolizumab. There were some injection-site reactions, but [these were] very manageable in patients who received IO102-IO103. The primary end point, of ORR was met [in patients with] HNSCC, and [the regimen] also showed favorable activity in NSCLC,” Reiss explained. “[A similar benefit was seen] when looking at the secondary end points such as progression-free survival; [results] compared favorably with single-agent pembrolizumab, but [these findings] will need to be confirmed in future randomized studies.”
In an interview with OncLive, Reiss expanded on the design of the basket trial and the implications of the findings. Reiss currently serves as the Medical Director of Thoracic Oncology at the University of California Davis Health in Sacramento.
Reiss: At ESMO this year, I presented [data from] a phase 2 basket trial of IO102-IO103, which is a vaccine against PD-L1 and IDO—an immunomodulatory peptide. [IO102-IO103] was given in conjunction with pembrolizumab in patients with advanced metastatic HNSCC and NSCLC. The rationale [for the study] was that there has been some promising data in melanoma, including
This single-arm basket [trial was designed] to probe for efficacy in PD-L1–high advanced squamous head and neck cancer and NSCLC.
In this basket trial, patients with advanced or metastatic NSCLC and HNSCC [were enrolled]. They were [required to have] PD-L1–high [tumors], where a standard of care is single-agent pembrolizumab. The idea was to use this immunomodulatory peptide [targeting] IDO and PD-L1 to make the tumors “hotter” and to determine whether this approach could elicit a stronger signal of activity in HNSCC and NSCLC.
In terms of some of the correlative studies that were done, patients who cleared their circulating tumor DNA tended to do better. We looked at gene expression signatures, and some findings could be prognostic, [but require further study]. The most important translational component that we presented was that patients developed antibodies to IDO and PD-L1 after vaccine administration.
We need to do randomized studies. [IO102-IO103 may] address an unmet need, even among patients with PD-L1–high HNSCC and NSCLC. There are patients [in these populations whose responses are suboptimal or of shorter duration], even though these are typically the target population for anti–PD-1 efficacy. There is still room for improvement [in the PD-L1–high populations], and we can also examine populations with lower PD-L1 expression.
