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Matulonis Highlights Early Promise Seen With Pembrolizumab/Mirvetuximab Soravtansine Combo in Ovarian Cancer

Danielle Ternyila
Published Online:1:44 PM, Fri April 6, 2018

Ursula A. Matulonis, MD
According to initial results presented at the 2018 Society of Gynecologic Oncology (SGO) Annual Meeting, 43% of the first 14 patients with platinum-resistant epithelial ovarian cancer treated with the combination of pembrolizumab (Keytruda) and mirvetuximab soravtansine (IMGN853), a folate receptor-alpha antibody drug conjugate (ADC), had partial responses. Additionally, 63% of patients treated with the combination who had moderate-to-high levels of folate receptor-alpha expression, the target of the ADC, had responses.

These results are quite exciting, as single-agent response rates in patients with platinum-resistant ovarian cancer are typically around 10%, says lead study investigator Ursula A. Matulonis, MD, who presented the findings during the meeting.

A total of 14 patients with a median of 4.5 prior lines of therapy were enrolled in the dose-escalation study. Mirvetuximab soravtansine was given at a starting dose of 5 mg/kg and then escalated to 6 mg/kg. Pembrolizumab was given at 200 mg.

Six of the 14 patients (43%; 95% CI, 18-71) had confirmed partial responses to the combination. Five of 8 (63%; 95% CI, 25-92) patients who had moderate-to-high levels of folate receptor-alpha expression had responses.

The median progression-free survival (PFS) was 5.2 months (95% CI, 1.6-9.5) in the entire cohort and 8.6 months (95% CI, 1.6-not evaluable) in the moderate-to-high cohort. The median duration of response was 30.1 weeks overall and 36.1 weeks in the patients with medium to high folate receptor-alpha expression.

Additional patients are now being enrolled on the trial, with a focus on women whose cancers have medium to high expression of the folate receptor-alpha protein.

In an interview with Targeted Oncology during the SGO meeting, Matulonis, medical director and program leader of Gynecologic Oncology at Dana-Farber Cancer Institute, highlighted the most significant findings of the study and discussed the future development of this agent.

TARGETED ONCOLOGY: Can you give an overview of this study and the significant findings?

Matulonis: The abstract that I'm presenting at this meeting involves the combination of an antibody-drug conjugate against the folate receptor-alpha called mirvetuximab soravtansine. This trial combined it with an immuno-oncology agent, pembrolizumab. There is also preclinical rationale for combining these 2 agents. In the abstract, we present the results of 14 patients who have been treated with this combination.

The first few were treated with a slightly lower dose of mirvetuximab soravtansine at 5 mg/kg, while the remainder of patients were treated with the higher dose in the standard single-agent phase of 2 doses of 6 mg/kg using pembrolizumab 200 mg. This trial entered all patients with varying levels of folate receptor-alfa expression. About 25% to 30% were low expressers and the remaining were medium to high expressers. When you look at the response rate of the entire population, it's about 43%, but if one pulls out the cancers that are medium to high expressers where we know that the single agent works better, the response rate actually goes up to 63%. This is quite exciting.

The other important feature is this is a heavily-pretreated population. The median number of prior lines for the entire 14 patients was 4.5 prior lines, so it is a very heavily pretreated platinum-resistant population. Right now, we are enrolling additional patients into this trial and really focusing on women whose cancers have medium to high expression of the folate receptor-alpha protein.

TARGETED ONCOLOGY: How do these results compare to the standard of care treatment for this population?

Matulonis: Sixty-three percent response rates are unheard of in platinum-resistant ovarian cancer. Typically, you would expect response rates of single-agent pegylated liposomal doxorubicin or single-agent topotecan (Hycamtin) to be around 10% or less.

TARGETED ONCOLOGY: What is your opinion of the safety profile of this combination?

Matulonis: We looked at the safety profile and at expected toxicities from either agent, mirvetuximab soravtansine or pembrolizumab. Thinking about that in combination and whether we are seeing any additional toxicities, one would think about pneumonitis being an issue, but in reality, there is no abnormal safety signal. This appears to be a very safe combination.

TARGETED ONCOLOGY: Do you have any specific patient experiences you can share?

Matulonis: I have personally treated a number of women on this combination. I have patients who are platinum-resistant, heavily pretreated with a number of prior lines, but what really impresses me about this combination is the quickness at which it starts to work. We have 2 recent patients treated at my institution who have platinum-resistant cancer, BRCA wild-type, who have cancers that have grown through platinum several times, and in both instances, we are seeing tumor regression after just 2 cycles of the combination. That's pretty exciting.

TARGETED ONCOLOGY: Where do you think the future development of this combination should focus next?

Matulonis: We'd love to see additional patients enrolled. We should really be focusing in on the efficacy of the combination in patients with platinum-resistant disease, which is an unmet need, and focusing on the medium to high expressers. If we can confirm that there is such a high response rate in this specific patient population, but more heavily pretreated, then I think that's a potentially really important patient population to go after.

TARGETED ONCOLOGY: Are there any other details about the design of this trial that you can share?

Matulonis: The other interesting part about this particular trial is that we are looking at pre- and post-biopsy, at pre-biopsy just before the patient starts the combination, and then another biopsy after she's been on it for a few weeks. I have no data to share on that, but I am very excited to see whether or not this combination can do anything to change the immune microenvironment, to maybe bring T cells into the cancer, so that's an exciting piece of this study that is a more translationally-focused piece that may also help to explain why we are seeing such profound responses with this combination.

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