The Targeted Pulse: The FDA Grants MB-105 ODD, and AI Helps Distinguish HER2 0 From 1+ in Breast Cancer

CAR T-Cell Therapy, MB-105, Gains Orphan Drug Designation in R/R T-Cell Lymphoma

MB-105, a first-in-class CD5-targeted chimeric antigen receptor T-cell therapy, has received orphan drug designation for the treatment of relapsed/refractory (R/R) CD5-positive T-cell lymphoma. In a phase 1 study (NCT03081910), MB-105 is undergoing evaluation in patients with T-cell acute lymphoblastic leukemia as well as R/R T-cell lymphoma, showing a promising overall response rate for those with T-cell lymphoma.

“The MB-105 phase 1 trial has shown promising safety and efficacy signals in patients with R/R T-cell lymphoma. This designation further validates our development strategy as we prepare to initiate our phase 2 clinical trial in early 2025,” said Sarah Hein, co-founder and chief executive officer of March Biosciences, in a news release. To explore the current data, access the full article here.

AI Tool Helps Improve Standardization of Scoring HER2 0 From 1+ in Breast Cancer

A new artificial intelligence (AI) tool assisted pathologists in distinguishing HER2 0 from 1+ in breast cancer cases, outperforming the Standard of Care/Gold standard. The AI tool is essential for keeping pathologists and clinicians abreast with targeted therapies and guidelines that differentiate treatment effectiveness based on HER2 status.

“We were surprised to find that the interobserver agreement among the pathologists was only about 72%, which is quite low,” said Manuela Vecsler, PhD, in an interview. “In the end, what the study showed was that by using AI, we can improve this interobserver agreement and, consequently, improve consistency and standardization of scoring.” For more details on this useful tool, access the full article here.

Zipalertinib Met ORR End Point in a Phase 2 Trial For EGFR+ NSCLC

In the phase 2b portion of the open-label, multicenter, first-in-human REZILIENT1 trial (NCT04036682), zipalertinib monotherapy achieved the primary end point of overall response rate in patients with non–small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutations. Enrolled patients had received prior therapy. Complete findings are expected to be presented at an upcoming international conference, and US regulatory approval expected to be sought in the second part of 2025.

The trial is separated into multiple sections: the phase 1 dose-escalation portion, the phase 2a dose-expansion portion, module A, module B, and module C. Findings from module C were presented at the ESMO Congress 2024. In the presentation, investigators reported that for heavily pretreated patients with NSCLC harboring EGFR exon 20 insertion mutations who progressed on or after amivantamab (Rybrevant), zipalertinib was well tolerated and demonstrated a manageable safety profile. For more background information, access the full article here.

Paclitaxel Showdown: Oral Bests IV for Overall Survival in Advanced Gastric Cancer

The oral solution of paclitaxel (Liporaxel) outperformed the intravenous (IV) solution in overall survival (OS) and was non-inferior in progression-free survival (PFS) for second-line advanced gastric cancer, according to data from a phase 3 clinical trial (CTR20190050). Between April 22, 2019, and the data cut-off of January 31, 2022, 536 patients were randomly assigned to receive either the oral solution (n=268) or the IV solution (n=268) of paclitaxel. However, in the primary analysis with a cut-off date of February 15, 2023, superior OS rates were observed in those receiving the oral solution. A poster presenting these data was featured at the 2025 ASCO Gastrointestinal Cancers Symposium.

The rationale for evaluating the oral solution of paclitaxel vs the IV solution as a second-line monotherapy was to establish non-inferiority in both efficacy and safety for patients with gastric cancer. The oral solution of paclitaxel demonstrated a favorable safety profile, supporting its potential as a second-line treatment option for this patient population, according to investigators. For detailed data, access the full article here.

T-DXd Scores an Approval in HR+, HER2-Low/Ultralow Breast Cancer

Fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) has received FDA approval for the treatment of adult patients with unresectable or metastatic, hormone receptor–positive, HER2-low or HER2-ultralow breast cancer that has progressed on 1 or more endocrine therapies in the metastatic setting. The HER2-low category is defined as an immunohistochemistry [IHC] score of 1+ or 2+/ISH- and HER2-ultralow as an IHC score of 0 with membrane staining. These assessments must be conducted using an FDA-approved test. The approval is supported by data from the phase 3 DESTINY-Breast06 trial (NCT04494425), which evaluated T-DXd against investigator’s choice of chemotherapy, showing an improvement in median PFS and favorable OS trends.

“In estrogen receptor-positive, metastatic breast cancer, whenever you are thinking of chemotherapy for a patient, that is where potentially T-DXd is an option, as seen in the DESTINY-Breast06 study,” said Aditya Bardia, MD, MPH, FASCO, professor in the Department of Medicine, Division of Hematology/Oncology, and director of Translational Research Integration at UCLA Health Jonsson Comprehensive Cancer Center, Los Angeles, CA, in an interview. For efficacy and toxicity data, access the full article here.

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

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