Clinical Trial Explores New FRα-Targeting ADC for Platinum-Resistant Ovarian Cancer

John Diaz, MD

With the FRα protein being overexpressed in approximately 80% of malignant ovarian tumors, oncologists who treat these patients find themselves in need of new therapeutic options. The novel FRα-targeting antibody-drug conjugate, STRO-002 is quickly advancing in the course of development to potentially offer a solution to the issue.

The advances observed with STRO-002 include a fast track designation granted by the FDA in August 2021 for the treatment of patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received 1 to 3 prior lines of systemic therapy. This announcement came shortly after early signals of efficacy were shown in 34 patients treated in a phase 1 clinical trial (NCT03748186) with STRO-002 at 2.9 mg/kg or higher.

In 31 evaluable patients, treatment with STRO-002 led to responses in 10 patients, including 1 complete response and 9 partial responses (PRs). At the time of data cutoff, there were also 6 patients with unconfirmed PRs. The disease control rate was 74%.

STRO-002 also showed early signs of tolerability in the phase 1 study. Grade 1 or 2 treatment-emergent adverse events (TEAEs) occurred in 86% of patients. No ocular toxicity had occurred by the data cutoff date, but prophylactic corticosteroid eye drops had been administered to patients. The most common grade 3/4 TEAE was neutropenia, which was reversible. Standard medication was also administered to the 15.4% of patients who experienced grade 3 arthralgia and the 7.7% who experienced neuropathy.

In an interview with Targeted Oncology™, John Diaz, MD, deputy chief of Gynecologic Oncology, director of Minimally Invasive Gynecologic Surgery, and lead physician of Clinical Research of Gynecologic Oncology at Miami Cancer Institute, Baptist Health South Florida, discussed the ovarian cancer treatment paradigm and the promise of STRO-002 for an important ovarian cancer subgroup.

TARGETED ONCOLOGY™: What does the treatment landscape currently look like for patients with ovarian cancer?

Diaz: Recently, we've had a lot of breakthroughs with the upfront treatment of ovarian cancer, particularly with the adoption of PARP inhibitors in the maintenance setting. So that's really changed the landscape on how we treat ovarian cancer and has helped to increase treatment-free survival and progression-free survival for patients. In other words, from the time that they finish their chemotherapy, to such time that they're going to require additional initiation of chemotherapy, their cancers come back.

The challenge has been finding out what happens when that cancer comes back, particularly when those patients become platinum resistant. So, for those patients with ovarian cancer, we really have limited options. We do have chemotherapy alone and chemotherapy in combination with bevacizumab [Avastin], but it's still really an area of great need for our patients. A lot of the focus on clinical research and clinical trials has been to try and develop new therapies for women with platinum-resistant ovarian carcinoma.

Recent data from the American Cancer Society shows that 6.3% of cancer deaths in Florida are related to ovarian cancer. Based on this fact, what is your statement about the importance of developing new therapies?

I think it's critically important because ovarian cancer is not very common. There is only about 22,000 cases a year. But it is the deadliest gynecologic cancer, in part because when ovarian cancer is diagnosed, over 85% of the time, it's diagnosed at an advanced stage. That makes it more difficult to treat. Despite the fact that it is often presented in the advanced stages, ovarian cancer in the initial setting is very sensitive to chemotherapy, so 85% of patients are able to be placed into an initial remission. The challenge becomes that most of those patients do have a recurrence, and at that time, it's when we face the challenges finding effective treatment.

The other challenge for the treatment of various cancers is because it's not that common. Most oncologists have limited experience in the management of disease, which is why it's so important for women who are diagnosed with ovarian cancer to find someone who specializes in the treatment of the disease or center that specializes in management ovarian cancer, so they can be offered the latest treatments as well as clinical trials to help improve their outcomes.

You are the principal investigator at Miami Cancer Institute for the phase 1 study of STRO-002. Can you provide background on how this study came about and what the key goals are?

We've been fortunate at the Miami Cancer Institute to have access to a new medication called STRO-002. There's a phase 1 trial evaluating this treatment in the management of patients with platinum-resistant ovarian carcinoma. So, we have participated in this trial, and enrolled several patients onto this phase 1 trial. Our initial results were presented recently, and because of the promise of these results, the FDA and granted a fast track designation to this drug. So that's been very exciting to see the response that we've seen, particularly in patients with platinum-resistant ovarian cancer, who again have limited treatment options.

What result have been reported so far?

The exciting part of this trial is this trial is looking at a new class of drugs, what we call an antibody-drug conjugates, or ADCs. The way I explain this drug to my patients is that it's a little bit like a Trojan horse. So, on the outside of these drugs, there are different receptors. This particular drug is an antifolate receptor, so it binds to cancer cells, particularly platinum-resistant ovarian cancer cells that tend have a lot of those receptors on their surface. So once the drug binds to that cancer cell, it then introduces that Trojan horse into the cell, and that's where it releases its payload or its drug, and that's where it has activity into that cell as well as the neighboring cells.

These results have been pretty exciting. They were recently presented, and it showed that the response rates for this medication were higher than we'd expect for medications in this class. And because of those encouraging results, with the decrease in CA-125 and seeing responses like stable disease, that the FDA granted fast track designation.

What is the current status of this study at Miami Cancer Institute?

The trial is still open. Again, we're very encouraged by the initial phase 1 results and we've increased the cohort and the number of patients that we’re enrolling into the trial.

We're hoping now with the FDA fast track that we can then move this drug along to further trials, phase 2, and potentially phase 3. The goal is to see exactly how effective it is in the treatment of platinum-resistant cancer and see if we can bring this drug to market sooner to help women with this disease.