Novel Immunomodulatory Vaccine Plus Pembrolizumab Shows Early Activity in PD-L1–High NSCLC Adenocarcinoma

Treatment with the first-in-class IO102-IO103 immunomodulating cancer vaccine and pembrolizumab (Keytruda) demonstrated early clinical activity in treatment-naive patients with metastatic, non–small cell lung cancer (NSCLC) adenocarcinoma with a PD-L1 tumor proportion score of 50% or greater, supporting the continued investigation of this regimen in the first line, according to Jonathan W. Riess, MD, MS.

At the 2023 IASLC World Conference on Lung Cancer, initial data from a phase 2 trial (NCT05077709) showed that treatment with this combination (n = 15) resulted in an overall response rate of 53.3% (95% CI, 26.6%-78.7%), which consisted entirely of partial responses (PRs); 26.7% of patients achieved stable disease and 20.0% experienced disease progression.

Study enrollment is ongoing, and longer follow-up of survival outcomes and duration of response is planned.

“We need to improve outcomes—even in patients with metastatic lung cancer who are PD-L1–high, and IO102-IO103 in combination with pembrolizumab is a promising strategy to do so,” said Riess, who is the medical director of Thoracic Oncology and an associate professor of Medicine in the Division of Hematology & Oncology, at University of California Davis Comprehensive Cancer Center, in Davis, California. “We await the updated data [from this study] with more patients.”

In an interview with OncLive^®, Riess discussed how prior data led to the investigation of IO102-IO103 in combination with pembrolizumab in patients with PD-L1–high NSCLC adenocarcinoma, detailed the initial efficacy and safety data reported in this population, and spotlighted other influential research in lung cancer presented at the meeting.

OncLive: What was the rationale for investigating the IO102-IO103 cancer vaccine in combination with pembrolizumab in the first-line setting for patients with NSCLC adenocarcinoma?

Riess: The rationale for this clinical trial is based on a vaccine for PD-L1 and IDO. The idea is to administer this vaccine with the immune checkpoint inhibitor pembrolizumab and [shift] the immune microenvironment from an immunosuppressive microenvironment to a more immunopermissive microenvironment. [In other words, we wanted to create] a pro-inflammatory tumor immune microenvironment.

Could you expand on any previously reported data that supported the inception of this phase 2 trial?

There were exciting data from a phase 1/2 study [NCT03047928] done in [patients with] melanoma [which showed] that the combination of IO102-IO103 and nivolumab [Opdivo] [produced] complete response rates of approximately 50%. These data were published in Nature Medicine. Based on [these findings], we extended testing of this combination of PD-1 [inhibitors] and IO102-IO103 in patients with lung adenocarcinoma and head and neck squamous cell cancer. What I presented [during the meeting] were data regarding patients who had PD-L1–high, advanced and metastatic NSCLC with lung adenocarcinoma histology who were treated with this combination.

What early efficacy and safety findings from this study were presented?

We had 15 evaluable patients. Those were patients who had received 2 or more cycles of treatment to give some time for the vaccine to work and who had 2 scans to confirm responses. The confirmed response rate was [53.3%], and 8 of these 15 patients had confirmed PRs. We’re excited about these data.

Overall, the systemic adverse effects [(AEs) with the combination] were in line with immune-related AEs that we see with single-agent pembrolizumab. The most common treatment-related AE is injection site reactions. [We] generally rotate where the patient is receiving the injection to help [alleviate] that.

What next steps are planned for this research?

The next steps are to get more patients. Only 15 patients were evaluable for efficacy, so we need to get more. [We] plan to enroll 30 evaluable patients with lung adenocarcinoma onto the trial, and we’re excited to see those updated results.

Were there any other research efforts that you were excited to see presented at the meeting?

It was interesting to see data from the [phase 3] FLAURA2 trial [NCT04035486] of chemotherapy and osimertinib [Tagrisso] vs osimertinib alone in [patients with] EGFR-mutant lung cancer with common mutations. Early [data showed a] PFS benefit [with this regimen] but did not show a clear trend toward [improved] OS. There may be unique populations that this combination may be right for, [but we are] still waiting for additional data [to help us identify] the specific, high-risk subsets that may benefit from the combination. There was some suggestion that [patients with] central nervous system metastases might be one of those subsets, but [we still don’t know] how ctDNA persistence and comutation influences outcomes where the combination may be better than single-agent [osimertinib]. I await those updated results.

The MARS2 study [NCT02040272] was also illuminating. It showed that randomly assigning patients to pleurectomy decortication actually did harm [to patients with mesothelioma]. That [procedure] has been [utilized] for a long time, and [these data] highlight the importance of doing randomized clinical trials. That [trial] was powerful and well presented.

Reference

Riess J W, Cohen E, Vuky J, et al. Phase 2 trial of IO102-IO103 vaccine plus pembrolizumab: preliminary results for the first-line treatment of lung adenocarcinoma. Presented at: 2023 IASLC World Conference on Lung Cancer; September 9-12, 2023; Singapore, Republic of Singapore. Abstract MA15.09.