The Targeted Pulse: New Approvals, Including Expanded Approvals, GEJ Treatment Debates, and More


The FDA approves T-DXd for HER2+ tumors; SynKIR-310 trials begin, and experts debate FLOT vs. CROSS in GEJ cancer in this week’s recap article.

Trastuzumab Deruxtecan is Launched, Receiving FDA Approval in HER2+ Solid Tumors

Trastuzumab deruxtecan-nxki (T-DXd; Enhertu) is now approved by the FDA for patients with inoperable or metastatic tumors expressing HER2, who have undergone prior systemic therapy, and who have no satisfactory alternative treatment options. The approval is based on data from 3 trials: DESTINY-PanTumor02 (NCT04482309), DESTINY-Lung01 (NCT03505710), and DESTINY-CRC02 (NCT04744831) trials. The tumor agnostic indication was given accelerated approval by the FDA and is supported by the objective response rate data from these trials.

“Trastuzumab deruxtecan is already known to be active as an antibody-drug conjugate and …it has efficacy in the setting of HER2-low, HER2-positive breast cancer, HER2-positive gastric cancer, and lung cancer,” Funda Meric-Bernstam, MD, explained in an interview with Targeted OncologyTM. Meric-Bernstam is chair of the Department of Investigational Cancer Therapeutics at MD Anderson Cancer Center in Houston, Texas.

Sketch of myeloma cells

Expanded Approval: 2 Prior Lines of Therapy for Ide-Cel in R/R Multiple Myeloma

The FDA has expanded its approval for idecabtagene vicleucel (ide-cel, Abecma) to include patients with relapsed or refractory multiple myeloma who’ve received 2 or more prior lines of therapy. Prior therapy includes an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. This expansion furthers ide-cel’s reach from the previous approval which included patient with 4 prior lines of therapy.

This approval is based on data from the phase 3 KarMMA-3 study (NCT03651128), which compared ide-cel with standard-of-care regimens. “Regarding the primary end point of the study which was progression-free survival, with the extended follow-up, ide-cel continued to show a significant improvement in progression-free survival,” Paula Rodriguez-Otero, MD, PhD, said. Rodriguez-Otero, MD, PhD, is associate clinical professor and deputy director of the Expert Degree in Immuno-Oncology at the University Clinic of Navarra in Pamplona, Spain.

Sketch of lymphoma cells in human lymph nodes

FDA Received an IND for SynKIR-310 in R/R B-Cell Non-Hodgkin Lymphomas

The FDA has received an investigational new drug application for the phase 1 trial evaluating the agent, SynKIR-310. Patients with relapsed/refractory B-cell non-Hodgkin lymphomas, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma are included in the trial. Those who are either naive to chimeric antigen receptor (CAR) T-cell therapy or who have previously received CAR T-cell therapy but have since relapsed or become refractory to it will be evaluated.

“We believe SynKIR-310, comprised of a split-chain KIR-CAR incorporating our novel DS191 binder, has the potential to prolong T-cell antitumor function, and improve persistence in patients with aggressive lymphomas, preventing early disease relapse. Initiation of the clinical trial is the culmination of years of focused research and diligent work by the Verismo team,” Laura Johnson, PhD, chief scientific officer of Verismo Therapeutics, said in the press release.

Sketch of human gastrointestinal tract

Experts Debate Regimens FLOT vs CROSS in Resectable GEJ Adenocarcinoma

At present, there are no established guidelines for prioritizing or selecting neoadjuvant therapies for use in the management of gastroesophageal junction (GEJ) adenocarcinoma. Addressing this gap, experts debated at the 2024 Society of Surgical Oncology Annual Meeting, about maximizing the optimal benefit between the FLOT and the CROSS regimens.

“We need to consider [that] …it is not just the location, but the [microsatellite instability (MSI)]-high status [that] should be considered. These patients should, even though they are not metastatic, their tumor should be evaluated for HER2, MSI-high, and PD-L1 status, which will become important in decision making,” Yanghee Woo, MD, said in an interview with Targeted OncologyTM regarding the debate. Woo is surgical oncologist in the Division of Surgical Oncology, associate professor in the Department of Surgery, vice chair of international affairs, director of the Gastroenterology and Minimally Invasive Therapies Program at City of Hope in Irvine, California.

Sketch of breast cancer

Antibody-Drug Conjugates Have Transformed HER2-Positive Breast Cancer Care

Antibody-drug conjugates (ADCs) revolutionize cancer treatment by precisely targeting chemotherapy to tumor cells, reducing off-target effects. Despite evolving challenges, ADCs such as trastuzumab emtansine (Kadcyla) and fam-trastuzumab deruxtecan-nxki (Enhertu) have become standard therapies for HER2-positive breast cancer, showing efficacy even in heavily treated patients. However, vigilant toxicity management is essential for optimizing treatment outcomes.

“We’re all going to be inundated with the efficacy data; that’s what gets us excited. That’s what garners the FDA approval, that’s what changes the standard of care,” Irene M. Kang, MD, said. “But just as important as knowing what the benefit is for your patients will be knowing what the potential toxicities are, because your patient can’t benefit from a drug if they can’t tolerate the drug.” Kang is medical director of women’s health medical oncology at City of Hope Orange County in Irvine, California,

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

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