Targeted Pulse: FDA Approves Mirvetuximab, Denies Odronextamab, and More

FDA Delivers 2 Complete Response Letters for Odronextamab in DLBCL

The FDA issued 2 complete response letters for the biologics license application for odronextamab (REGN1979). The agent was evaluated for patients with relapsed/refractory follicular lymphoma and relapsed/refractory diffuse large B-cell lymphoma after 2 or more lines of systemic therapy. The letters were in response to the enrollment status of confirmatory trials evaluating the agent. However, no issues were discovered regarding efficacy or safety or with the trial design, labeling, or manufacturing.

“Odronextamab is a CD3×CD20 antibody that directs T-cell function against B-cell malignancies. It showed significant clinical efficacy in a phase 1 trial. ELM-2 [NCT03888105] is a phase 2 trial looking at both diffuse large B-cell lymphoma and follicular lymphoma,” Jon E. Arnason, MD, said. Arnason is a physician scientist at Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Evaluating New Treatment Options in Myelofibrosis Management

The introduction of JAK inhibitors such as fedratinib (Inrebic), momelotinib (Ojjaara), and pacritinib (Vonjo) has significantly broadened treatment options for patients with myelofibrosis. In this evolving landscape, monitoring for potential adverse events associated with these tailored agents becomes more crucial. Further, the emergence of BET and BCL-xL inhibitors, PIM kinase inhibitors, and promising immunotherapies signals more promising developments in the treatment landscape.

“We are in a situation where there are a lot of novel and interesting therapies. Right now, phase 3 data have just [been] reported out on pelabresib, which is a BET inhibitor, as navitoclax, which is the BCL-xL inhibitor, [and] both look really promising,” Raajit K. Rampal, MD, PhD, explained. Rampal is a hematologic oncologist at Memorial Sloan Kettering Cancer Center in New York.

Mirvetuximab Receives Full FDA Approval for Platinum-Resistant Ovarian Cancer

Mirvetuximab soravtansine-gynx (Elahere) has been granted full FDA approval for the treatment of platinum-resistant ovarian cancer with high folate receptor alpha (FR⍺) expression. The approval includes patients who have received 1 to 3 prior lines of treatment, and the phase 3 MIRASOL trial (NCT04209855) data were the basis for the approval. In the study mirvetuximab was compared with investigator’s choice of chemotherapy.

“As the first treatment to show a statistically significant overall survival benefit in patients with platinum-resistant ovarian cancer, Elahere provides an effective new option for patients with [FR⍺] positive tumors. These patients previously had very limited options and Elahere changes that,” Kathleen Moore, MD said. Moore is the deputy director and associate director of clinical research at the Stephenson Cancer Center of The University of Oklahoma and MIRASOL principal investigator.

Avutometinib Combo Shows High Response in Heavily Pretreated Ovarian Cancer

Avutometinib (previously VS-6766) plus defactinib showed high response rates in heavily pretreated patients with recurrent low-grade serous ovarian cancer. The data from the subgroup analysis from part A of the phase 2 ENGOT-ov60/GOG-3052/RAMP 201 trial (NCT04625270) showed that responses occurred in 3 out of 4 patients who had previously received MEK inhibitors.

“Notably, tumor regression was observed in the majority of patients, including those with stable disease or progressive disease with last line of therapy including previous MEK inhibitors,” Susana N. Banerjee, MBBS, MA, PhD, FRCP, and colleagues wrote in the presentation during the 2024 SGO Annual Meeting on Women’s Cancer. Banerjee is a consultant medical oncologist and research lead of the Gynecology Unit at The Royal Marsden NHS Foundation Trust, as well as a professor in women’s cancers at the Institute of Cancer Research in London.

The Impact of The Lifileucel Approval For Melanoma Therapy

With the approval of lifileucel (LN-44; Amtagvi) for patients with melanoma, especially those with advanced stages of the disease, the management of melanoma has taken a significant step forward. Howard D. Edington, MD, and Omid Hamid, MD, discussed what this step means for the field and how it’s impacting trial designs.

“The impact to the future of melanoma treatment is huge for lifileucel and other TIL [tumor-infiltrating lymphocyte] therapies... There is a TILVANCE trial [NCT05727904], which is a phase 3, randomized trial between single-agent PD-1 vs PD-1 and TIL. That will give us a lot of information about the earlier roles of these therapies,” Hamid explained. Hamid is chief of translational research and immunotherapy and director of melanoma therapeutics at The Angeles Clinic and Research Institute in Los Angeles, California.

“The observation that some primary melanomas disappear completely in patients was one that had been known for many years, but it [lifileucel] clearly suggested that patients were able to get rid of their own cancer," Edington stated. Edington is the director of the Melanoma and Skin Cancer Center at Allegheny Health Network in Pittsburgh, Pennsylvania.

Thank you for joining us for this week’s Targeted Pulse. Look out for more recaps to come.