Merus’ MCLA-128 antibody has helped patients with HER2-positive metastatic breast cancer who failed several lines of HER2 inhibitor therapy, according to initial results of a Phase 1/2 clinical trial.
One of the 11 patients achieved a partial response to the treatment that lasted more than eight months. Seven patients’ disease became stable — and in four of the seven it was stable more than five months. The clinical benefit rate of the treatment was 64 percent. This means that 64 percent of patients either responded to treatment or achieved a stable disease for at least 12 weeks.
MCLA-128 is a bi-specific antibody that targets both the HER2 and HER3 proteins associated with breast cancer. The Phase 1/2 trial is the first test of the therapy in humans.
Merus agreed to present the Phase 1 part of the trial’s results at the American Society of Clinical Oncology Annual Meeting in Chicago, June 2-6. Its poster-session presentation is titled “First-in-human phase 1/2 study of MCLA-128, a full length IgG1 bispecific antibody targeting HER2 and HER3: Final phase 1 data and preliminary activity in HER2+ metastatic breast cancer (MBC).”
“These clinical results demonstrate that single agent MCLA-128 is active and well tolerated in heavily pretreated metastatic breast cancer patients,” Dr. Josep Tabernero, head of Medical Oncology at Vall d’Hebron University Hospital, said in a press release. “This positions MCLA-128 as a promising agent for further development as combination therapy in the treatment paradigm of metastatic breast cancer. I look forward to seeing how these results translate in the planned Phase 2 combination studies.”
The Phase 1/2, open-label, multi-center, multinational, dose escalation trial (NCT02912949) is assessing the effectiveness, safety, tolerability, and immunogenicity of MCLA-128 in solid tumors. Immunogenicity is a therapy’s ability to provoke an immune response.
In Part 1 of the trial, which has been completed, patients received escalating doses of MCLA-128 to establish a maximum tolerated dose and a Phase 2 dose.
Nine of the 11 patients in Phase 1 received 750 mg of MCLA-128 every three weeks, and two received 480 mg every three weeks. Researchers chose 750 mg as the Phase 2 dose.
The patients in the Phase 1 part of the trial had received a median of six previous lines of therapy for metastatic cancer before being treated with MCLA-128. This included two to five previous anti-HER2 therapies per patient.
A larger patient group will be used in Phase 2., which will evaluate MCLA-128’s safety in combo treatments for metastatic cancers, or those that have spread. The mix will include breast, ovarian, gastric, endometrial, and lung cancers.
One combo to be tested is MCLA-128, Herceptin (trastuzumab) and chemotherapy in HER2-positive metastatic breast cancer patients whose disease failed to respond anti-HER2 therapies.
Another combo will be MCLA-128 and Faslodex (fulvestrant) in hormone receptor-positive, HER2-low metastatic breast cancer patients whose disease failed to respond to hormone therapies and CDK4/6 inhibitors.
Phase 2 is expected to begin in the second half of 2017. It will be conducted in the United States and Europe. Merus is currently enrolling patients for it.
“With demonstrated activity in an aggressive disease population, our goal now is to understand where MCLA-128, in combination with current standards of care, can address unmet needs in this disease and deliver improved outcomes and greater optionality to patients in need,” said Dr. Ton Logtenberg, chief executive officer of Merus. “We see opportunities in HER2-positive MBC and hormone-resistant estrogen receptor positive MBC, where escape from hormone therapy is often via HER2/3 signaling. We also look forward to continuing to evaluate MCLA-128 in other tumor types, including endometrial, ovarian, gastric and NSCLC [non-small lung cell] cancers in this ongoing study.”