Olvi-Vec Plus Chemo Yields Disease Control in Platinum-Relapsed or -Refractory ES-SCLC

Olvi-Vec Plus Chemo in ES-SCLC:

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The addition of the modified oncolytic vaccinia virus olvimulogene nanivacirepvec (olvi-vec; GL-ONC1) to platinum-based chemotherapy and etoposide led to disease control in patients with platinum-relapsed or -refractory extensive-stage small cell lung cancer (ES-SCLC), according to preliminary data from the phase 1b/2 Olvi-Vec-SCLC-202 trial conducted in China.

Findings announced by Genelux, showed that evaluable patients (n = 7) achieved a disease control rate of 71%, including 2 patients who experienced a partial response per RECIST 1.1 criteria. One patient treated in the dose-escalation cohort achieved a tumor reduction of approximately 79% and remained on treatment at the data cutoff. The 3 patients to experience stable disease (SD) were treated in the lower-dose cohorts and had tumor reductions ranging from 24% to 29.2%.

Olvi-vec plus chemotherapy showed a manageable and tolerable safety profile that was consistent with that of prior studies. Most treatment-related adverse effects (TRAEs) were mild to moderate; the most common TRAEs comprised fever, anemia, reduced lymphocyte count, and nausea. The maximum tolerated dose was not yet reached.

“We are encouraged by the phase 1b trial data which suggest preliminary antitumor activity. Consistent reductions in all individual target lesions in participants experiencing disease control [n = 5/7], combined with encouraging antitumor activity of the first evaluable participant in the most recent dose-escalation cohort, highlights the potential of systemically administered olvi-vec to provide meaningful clinical benefit for patients with relapsed or refractory ES-SCLC,” Thomas Zindrick, president, CEO, and chairman of Genelux, stated in a news release. “These results are consistent with our previous phase 2 [trial (NCT02759588)] results in platinum-resistant/refractory ovarian cancer and, with further investigation in our ongoing trials in relapsed/refractory lung cancer, we anticipate demonstrating the potential of olvi-vec as a platinum-resensitizing immunotherapeutic agent across multiple types of recurrent cancers with significant unmet medical needs.”

Olvi-vec is a stable DNA virus with a large engineering capacity. Based on preclinical data where olvi-vec demonstrated the ability to infect and directly kill a wide range of tumor cell types both in vitro and in vivo, the agent is being evaluated for the treatment of patients with multiple types of cancer across various clinical trials.

Olvi-Vec-SCLC-202 is an open-label, multicenter trial being conducted at Shanghai Chest Hospital and Zhejiang Provincial People's Hospital in China. The study is evaluating the safety, tolerability, pharmacokinetics, and efficacy of olvi-vec plus chemotherapy in patients with platinum-relapsed or -refractory ES-SCLC.

Enrolled patients receive a single cycle of olvi-vec administered on 3 consecutive days. Twenty-one days after the final dose of olvi-vec, patients are given platinum-based chemotherapy plus etoposide. Treatment continues until disease progression or unacceptable toxicity.

The dose-escalation portion of the study is evaluating increasing doses of olvi-vec to determine the recommended phase 2 dose (RP2D). In dose expansion, olvi-vec could be combined with other agents, such as immune checkpoint inhibitors, if safety data support exploring additional combinations. In the phase 2 portion, investigators will further evaluate the safety, tolerability, and efficacy of olvi-vec at the RP2D.

Among the 7 patients treated in the trial thus far, all had documented disease progression at the time of enrollment. One of the patients to experience SD received 3 prior lines of therapy.

"The initial results are promising, especially considering the challenging and fragile nature of this patient population with [ES-SCLC] and poor prognosis. What stands out is the antitumor responses in these participants, some who have been heavily pretreated and have [progressed on] prior platinum-based therapy, which offers significant potential for olvi-vec to provide meaningful clinical benefits in SCLC, even in a patient population with complex and late-stage disease,” Benny Li, PhD, CEO of Newsoara, the drug’s Chinese co-developer, added in a news release. “Ongoing evaluation of the phase 1b results is consequentially informing the design elements of the phase 2 portion of the clinical trial."

Reference

Genelux and Newsoara announce positive preliminary phase 1b/2 data of olvi-vec in advanced small-cell lung cancer. News release. Genelux. March 25, 2025. Accessed March 25, 2025. https://investors.genelux.com/news-releases/news-release-details/genelux-and-newsoara-announce-positive-preliminary-phase-1b2