Early Data for CRX100 Pave Way for Potential Combinations in Recurrent, Platinum-Resistant Ovarian Cancer

Preliminary data for CRX100—an adoptive natural killer–like T (NKT)–cell therapy combined with an oncolytic virus—indicate that this treatment could alter the tumor microenvironment to improve responses to other therapies in patients with recurrent, platinum-resistant ovarian cancer, according to Oliver Dorigo, MD, PhD.

Data from a phase 1 trial (NCT04282044) presented at the 2024 SGO Annual Meeting on Women’s Cancer showed that no dose-limiting toxicities were observed with CRX100 monotherapy in 7 patients. The most common adverse effect was mild fever that occurred 6 to 12 hours after infusion.

Additionally, 5 of 7 patients remained alive between 1 and 36 months following CRX100 infusion, with 2 patients succumbing to progressive disease. Notably, 1 patient who was administered 2 infusions of CRX100 3 months apart experienced stable disease after the first dose. Twenty-six weeks following the second infusion with the NKT-cell therapy, this patient’s CA125 serum marker level decreased from 20,435 U/mL to 11,538 U/mL. The CA125 level was further reduced to 296 U/mL following subsequent treatment with an investigational antibody-drug conjugate combined with pembrolizumab (Keytruda).

“This is a very telling patient [whose response data] suggest to us that the virus sets up a tumor microenvironment that might be more conducive to better antitumor responses with follow-up therapies, in particular immunotherapies,” Dorigo said in an interview with OncLive^®.

In the interview, Dorigo expanded on the background for CRX100; highlighted the key findings derived from the phase 1 study thus far; and detailed the next steps for investigating this agent as a potential treatment for patients with recurrent, platinum-resistant ovarian cancer.

Dorigo is an associate professor of gynecologic oncology, director of the Stanford Gynecologic Oncology Fellowship, director of the Stanford Clinical Research Group for Gynecologic Cancer Trials, director of the Stanford Gynecologic Oncology Clinical Care Program, director of the Mary Lake Polan Gynecologic Oncology Research Laboratory, and director of Stanford Obstetrics and Gynecology, Division of Gynecologic Oncology, in California.

OncLive: What is CRX100, and what was the rationale for investigating this agent as a treatment for patients with recurrent, platinum-resistant ovarian cancer?

Dorigo: CRX100 is a new cell therapy that delivers an oncolytic virus to tumor cells in patients with ovarian cancer. The cells we are using are not traditional T cells, as commonly used in cell therapies; rather, [we use] the cell population that are called NKT cells. NKT cells are a hybrid cell population that have features of both NK and T cells. They have distinct features that [could] work to our advantage when it comes to tumor immune responses.

The virus that the cells are delivering is a vaccinia virus, and it's genetically modified to only replicate in tumor cells. When the virus infects normal cells, it is not supported in its replication. Therefore, normal cells are spared from the cytolytic toxicity of the oncolytic virus. Therefore, because of this genetic modification of the virus, it is a tumor-specific therapy, and it is exciting because it could reduce the off-target AEs.

How was this study of CRX100 conducted?

At [the 2024 SGO Annual Meeting on Women’s Cancer], we presented [data] on our first 7 patients with ovarian cancer treated with [CRX100] that delivers the oncolytic virus. CRX100 was delivered in a dose-escalation scheme. We kept the number of cells constant for each patient at 3 x 109 cells. These cells were generated by leukapheresis from patients, and we then expanded the cell product in the laboratory. When enough cells were obtained, they were infected with the virus about 24 hours prior to infusion into the patient. We escalated the dose of the virus ranging from 3 x 107 plaque forming units [PFU] to 3 x 109 PFU.

What key safety findings from the trial were presented at the 2024 SGO Annual Meeting on Women’s Cancer?

What we observed, in general, is that this therapy is very well tolerated. It does not require lymphodepletion at this point. We saw some patients with elevated temperatures a few hours after the infusion of the cell product. [Elevated temperature] is an AE of cell therapy that is fairly common. We can mitigate this with simple measures, such as acetaminophen given prior to the cell infusion. In general, patients tolerated the infusion very well.

What was found regarding efficacy?

In terms of antitumor effects, we had 2 patients that we felt had a very favorable response. Particularly, in 1 patient who received 2 infusions [3 months apart], a few months after the [second] infusion, she had a significant decrease in her CA125 serum marker level. It reduced to [11,538 U/ml] from here [20,435 U/ml] pretreatment level. In addition, this patient had follow-up therapies that included pembrolizumab and had a very significant response to this immunotherapy.

What are the next steps for investigating CRX100 in patients with ovarian cancer?

We are excited and encouraged by these data, and in the next iteration of this trial, we will combine CRX100 with pembrolizumab. Additionally, we built into the next phase of the trial a step where we use lymphodepletion that will precede the infusion of CRX100, potentially in combination with pembrolizumab. We are looking for optimization of the antitumor effects in the next phase of development.

Reference

Dorigo O, Patel S, Moser J, Frohlich M, Contag P. Safety and tolerability of CRX100, an NKT cell therapy combined with tumor-specific oncolytic vaccinia virus among patients with recurrent, platinum-resistant ovarian cancer. Presented at: SGO 2024 Annual Meeting on Women’s Cancer; March 16-18, 2024; San Diego, CA.