STRO-002, Sutro Biopharma’s experimental antibody-drug conjugate, continues to be safe and elicit promising responses in heavily pretreated patients with advanced ovarian cancer, according to the latest data from a Phase 1 clinical trial.
Updated interim findings from the ongoing open-label study (NCT03748186) showed that 32% of women who were eligible for response analyses responded to STRO-002, when given at doses of 2.9 mg/kg or higher.
“We are encouraged to see meaningful clinical benefit from STRO-002 for patients with advanced platinum-resistant and refractory ovarian cancer. The women on the study are heavily pretreated and have limited treatment options as many have received experimental agents and participated in other clinical trials,” Lainie P. Martin, MD, said in a press release. Martin is a trial investigator and leader of the Gynecology/Oncology Program at the Hospital of the University of Pennsylvania,
“The deepening of responses in patients as well as disease control over time demonstrates STRO-002 to be an important potential treatment option for patients with ovarian cancer,” Martin added.
The findings were presented recently by Sutro during a virtual discussion with key opinion leaders.
STRO-002 is an antibody-drug conjugate made up of an antibody that specifically binds to folate receptor alpha, a protein found at high levels in most types of ovarian cancer. When the antibody binds to its target, it triggers the release of a toxic compound that destroys cancer cells, while sparing healthy cells.
The safety, tolerability, and preliminary efficacy of STRO-002 are being investigated in the Phase 1 trial, which is enrolling heavily pretreated women with recurrent advanced platinum-resistant or refractory ovarian cancer (including fallopian and primary peritoneal cancer) and endometrial cancer.
The trial is divided into two parts: an initial dose-escalation part, in which patients receive increasing doses (0.5–6.4 mg/kg given in 21-day cycles) of the therapy to determine its optimal recommended dose; and a dose expansion part, in which participants will receive the optimal dose of STRO-002 as determined in the previous phase of the trial.
Interim trial data announced earlier this year showed that eight of the 33 women (24%) who had been treated with STRO-002 and were eligible for response assessments, responded at least partially to treatment. Moreover, 13 patients also attained disease stabilization, for a disease control rate of 60% after a minimum of 12 weeks of treatment.
Safety assessments also indicated STRO-002 was safe and well-tolerated, with nearly all (87%) reported side effects being only mild or moderate in severity.
Updated interim data presented by the company confirmed the therapy’s favorable safety profile and ability to trigger promising responses in this patient population.
As reported, a total of 39 heavily pretreated women (2–11 prior lines of therapy) enrolled in the study’s dose escalation phase, and 34 received STRO-002 at a dose of 2.9 mg/kg or higher.
As of Oct. 30, 10 of the 31 women (32%) who were eligible for response assessments, responded favorably to treatment. From these, nine attained a partial response (tumor shrinkage) and one a complete response (complete cancer elimination).
Three of the nine women who achieved a partial response had a confirmed treatment response, including a 57-year-old woman with platinum resistant ovarian cancer who saw her tumor shrink by 74% after completing four treatment cycles.
An additional 13 patients also achieved a state of stable disease, amounting to a disease control rate of 74% following a minimum of 12 weeks of treatment — an outcome that is considered clinically relevant in this patient population.
Four women (13%) participating in the study already completed one year of treatment, and three of them (9.7%) are still receiving STRO-002. Apart from these, seven other women are still being dosed.
“We are seeing improved outcomes in disease control and … responses as the data matures and will continue to follow the patients who remain on study for further deepening of responses or clinical benefit,” said Arturo Molina, MD, chief medical officer of Sutro.
Safety assessments showed STRO-002 continued to be safe and well-tolerated, with nearly all (86%) reported adverse events (side effects) related to treatment being mild or moderate in severity.
Reversible neutropenia (low white blood cell counts) was the most common severe or life-threatening side effect observed to date. Severe joint and nerve pain were managed with standard treatments, which included some cases of dose reductions or delays that did not affect STRO-002’s effectiveness.
Supported by these promising early findings, Sutro now is planning to move ahead with the study’s dose expansion phase, which aims to generate data from ovarian cancer patients who received one to three lines of prior therapy, as well as in those with relapsed or refractory endometrial cancer.
Findings from this second portion of the trial also are expected to inform the design of a future registrational study of STRO-002.
“Additional data from the dose-expansion will inform regulatory discussions, accelerate registration strategy, and identify the broadest population that may benefit from STRO-002,” said Bill Newell, CEO of Sutro.
Ovarian cancer patients in the dose expansion portion of the study will be assigned randomly to receive STRO-002 at a dose of 4.3 mg/kg or 5.2 mg/kg. About 20 women are expected to enroll in each dose group. Patient dosing is expecting to start in January, with preliminary data expected by the second half of 2021.
A second group of 15–40 women with endometrial cancer will be included in the study’s dose expansion part. These patients also will receive STRO-002 at doses ranging from 4.3 mg/kg to 5.2 mg/kg. Dosing in this group is anticipated to start next year.
The company is planning to hold an end-of-Phase 1/2 meeting with the U.S. Food and Drug Administration in the second half of 2021 to discuss the regulatory development of STRO-002.