The Targeted Pulse: Clinical Advancements and FDA News

Welcome to this week's edition of The Targeted Pulse. This week in oncology, we saw a number of significant developments, from FDA approvals to promising clinical trial data for various cancer types. Here is a summary of the top stories.

FDA Grants Priority Review to Gedatolisib for Advanced Breast Cancer

The FDA has granted priority review to the new drug application (NDA) for gedatolisib, a first-in-class multi-target PI3K/mTOR inhibitor, for hormone receptor–positive/HER2-negative, PIK3CA wild-type advanced breast cancer.

The application, reviewed under the Real-Time Oncology Review program, is supported by the phase 3 VIKTORIA-1 trial. Results demonstrated a significant progression-free survival (PFS) benefit: the gedatolisib triplet (with fulvestrant [Faslodex] and palbociclib [Ibrance]) achieved a median PFS of 9.3 months vs 2.0 months for fulvestrant alone (HR, 0.24). The doublet also showed superiority (7.4 months; HR, 0.33). Common adverse events (AEs) included stomatitis and neutropenia, with notably low rates of grade 3/4 hyperglycemia. The Prescription Drug User Fee Act date is July 17, 2026.

New OrigAMI-1 Data Signal Shift Beyond First-Gen EGFR Inhibitors in Metastatic CRC

Updated results from the phase 1b/2 OrigAMI-1 study, presented at the 2026 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, evaluate amivantamab (Rybrevant)—a bispecific EGFR/MET antibody—in combination with FOLFOX/FOLFIRI for RAS/BRAF wild-type metastatic colorectal cancer.

In EGFR-naive patients, the combination achieved a 51% overall response rate (ORR) and a 7.5-month median PFS, with a median duration of response of 9.3 months. Notably, patients with liver metastases demonstrated a 57% ORR and an 11.3-month median PFS. Amivantamab aims to overcome resistance to first-generation EGFR inhibitors through dual receptor blockade and immune-mediated activity. Safety was manageable, primarily involving rash and neutropenia. Phase 3 trials (OrigAMI-2/3) are ongoing.

FDA Grants BTD to Sofetabart Mipitecan for Platinum-Resistant Ovarian Cancer

The FDA has granted breakthrough therapy designation to sofetabart mipitecan (LY4170156), a novel folate receptor alpha (FRα)-targeted antibody-drug conjugate (ADC) with an exatecan payload, for platinum-resistant ovarian cancer.

The designation is based on phase 1a/b data showing a 45% to 50% ORR and 74% to 78% disease control rate across all FRα expression levels, including patients previously treated with mirvetuximab soravtansine-gynx (Elahere). At the 4 mg/kg dose, the ORR reached 55%. Safety data indicate a manageable profile with no grade 3 ocular toxicity or peripheral neuropathy. The phase 3 FRAmework-01 trial is currently evaluating sofetabart mipitecan in patients with platinum-resistant ovarian cancer and platinum-sensitive disease.

Epcoritamab Monotherapy Yields Positive Results in Phase 3 R/R DLBCL Trial

Topline results from the phase 3 EPCORE DLBCL-1 trial demonstrate that subcutaneous epcoritamab monotherapy significantly improves PFS in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). In this global study of 483 transplant-ineligible patients (73% with ≥2 prior therapies), epcoritamab demonstrated an improvement in PFS in patients receiving epcoritamab monotherapy (HR, 0.74; 95% CI, 0.60-0.92).

While secondary end points showed improvement, overall survival did not reach statistical significance (HR, 0.96). The safety profile remained consistent with prior data, primarily involving manageable cytokine release syndrome and neutropenia. This is the first phase 3 trial to validate bispecific monotherapy in R/R DLBCL.

EMA Validates T-DXd for First-Line HER2+ Metastatic Breast Cancer

The European Medicines Agency (EMA) has validated a Type II Variation application for fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) in combination with pertuzumab (Perjeta) for the first-line treatment of HER2-positive metastatic breast cancer. This follows a recent FDA approval for the same indication.

The application is supported by the phase 3 DESTINY-Breast09 trial, which demonstrated a statistically significant improvement in PFS. The T-DXd triplet combination reached a median PFS of 40.7 months compared with 26.9 months with standard-of-care pertuzumab and trastuzumab (Herceptin) plus a taxane (docetaxel or paclitaxel). The safety profile was manageable; common AEs included nausea and neutropenia, with a continued need for monitoring for interstitial lung disease.