A new antibody to help treat certain cancers

A new antibody conjugate could be useful to personalize the treatment of patients with recurrent epithelial ovarian cancer who express the FolR-alpha protein.

Preliminary results from the phase I clinical trial STRO-002-GM1 of dose expansion of the antibody conjugate (ADC) Luveltamab tazevibulin (luvelta) demonstrate significant clinical benefits at the two doses tested in patients with recurrent epithelial ovarian cancer with expression levels of folate receptor alpha protein (FolR-alpha) greater than 25%.

Dr. Ana Oaknin, head of the Gynecological Neoplasms Group at the Vall d’Hebron Institute of Oncology (VHIO) and medical oncologist at the Vall d’Hebron University Hospital in Barcelona, ​​recently presented the results at a congress of the American Society of Oncology, held in Chicago, USA.

The folate receptor alpha (FolR-alpha) is involved in cell proliferation. Under normal conditions it is expressed at low levels in some organs. However, high levels of FolR-alpha have been observed in various malignancies, such as ovarian cancer, endometrial cancer, and non-small cell lung cancer (NSCLC), among others. “FolR-alpha overexpression in solid tumors favors tumor cell growth and is persistent in metastatic or recurrent tumors and after treatment. All these reasons make FolR-alpha a clinically relevant target for the treatment of ovarian and endometrial cancers” explains Dr. Ana Oaknin, who heads the research team.

Luveltamab tazevibulin is a novel antibody conjugate targeting FolR-alpha that induces cytotoxic and immunologic cell death. Using targeted conjugation technology, this drug is designed to target a wide range of ovarian tumors that express FolR-alpha.

Ana Oakin. (Photo: VHIO).

The clinical trial included 44 patients with advanced ovarian cancer who developed progressive platinum resistance (PROC) after 1 to 3 prior lines of treatment or platinum-sensitive disease after 2 to 3 prior lines of platinum-containing chemotherapy.

“Although the presence of the FolR-alpha protein was not required to participate in the trial, it was retrospectively analyzed to see if overexpression of this protein could be used to select patients,” says Dr. Oaknin.

Of the 44 patients included in the trial, half of them were treated with the 4.3 mg/kg dose and the other with the 5.2 mg/kg dose. 33 of the total number of patients had a concentration of FolR-alpha greater than 25%.

Results from the Phase I STRO-002 dose expansion study demonstrate that patients selected for greater than 25% FolR-alpha expression experienced significant clinical benefit, with an overall response rate of 37.5%. This response was even higher, 44%, if the patients received the high dose of treatment and their tumor expressed FolR-alpha greater than 25%.

The most common adverse events included neutropenia, arthralgia, and anemia, which were managed with standard medical therapy and dose reductions. Neutropenia had a higher incidence at the 5.2 mg/kg dose than at the 4.3 mg/kg dose. At high treatment doses, although treatment-related adverse events required a dose reduction in 76% of patients, only 1 patient had to discontinue treatment for such effects.

“In conclusion, these dose expansion data confirm the activity of luveltamab tazevibulin (luvelta) at starting doses ranging from 4.3 to 5.2 mg/kg in patients with recurrent ovarian cancer with FolR-alpha expression of more than 25% and support additional clinical studies in this population” says Dr. Ana Oaknin. “In fact, a global phase 2/3 study is already planned, in which the VHIO will act as European coordinators, which will evaluate luveltamab tazevibulin in patients with platinum-resistant ovarian cancer and with an intensity of FolR-alpha expression. greater than 25%”. (Source: Vall d’Hebron University Hospital / VHIO)