The Targeted Pulse: Biggest Oncology Developments of the Week

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 are the top 5 stories that shaped the week.

Biomarkers, Oncolytic Viruses, and the Promise of Personalized Treatment for Glioblastoma

Oncolytic virus therapy using Delta-24-RGD offers a novel approach to treating glioblastoma by selectively infecting tumor cells and eliciting a "bystander" immune response. Data from the phase 1 TARGET trial indicate that combining this virus with subcutaneous interferon-gamma significantly extends survival compared to viral monotherapy. Researchers identified 2 specific blood-based biomarkers—activated CD8+ natural killer T-cell signatures and high antiviral antibody titers—that correlate with long-term survival. These noninvasive markers enable clinicians to identify responders early through routine blood draws rather than risky brain biopsies. Such findings facilitate personalized dosing strategies, allowing for treatment escalation in responders or timely transitions for nonresponders.

CAR T Achieves 100% MRD Negativity in Newly Diagnosed Multiple Myeloma

The phase 2 CAREMM-001 trial demonstrated that the BCMA-directed chimeric antigen receptor (CAR) T-cell therapy YK-hBCMA BB-002 achieved 100% minimal residual disease (MRD) negativity at 3 months in transplant-ineligible patients with newly diagnosed multiple myeloma. Following short-course induction with VRd or daratumumab (Darzalex)-based regimens, the therapy produced a 94.4% complete response rate at the last follow-up. With a median follow-up of 15.8 months, no disease progression or MRD recurrence was observed. The safety profile was manageable, featuring expected hematologic toxicities and low-grade cytokine release syndrome. These results suggest that frontline CAR T-cell therapy can induce exceptionally deep, durable remissions in high-risk, underserved populations.

Role of Dual Maintenance Remains Uncertain in Multiple Myeloma

The landscape of maintenance therapy in newly diagnosed multiple myeloma continues to evolve as clinicians weigh the benefits of intensifying treatment against potential toxicities. While single-agent lenalidomide (Revlimid) remains the established standard of care following autologous stem-cell transplantation, the role of dual maintenance regimens is a subject of ongoing clinical debate. Data from trials like FORTE and AURIGA suggest that adding a proteasome inhibitor or an anti-CD38 antibody can significantly improve progression-free survival (PFS) and MRD conversion, especially in high-risk patients. However, these efficacy gains must be balanced against the increased risks of cumulative toxicity, cytopenias, and second primary malignancies. Experts emphasize that while quadruplet induction therapy is becoming standard, the definitive long-term survival benefit of dual maintenance for standard-risk patients is not yet fully established, leaving the optimal regimen and duration uncertain.

Varsetatug Masetecan Exhibits Early Efficacy, Safety in Late-Line Colorectal Cancer

Interim data from the phase 1 CTMX-2051-101 study demonstrate encouraging clinical activity for varsetatug masetecan (Varseta-M), an EpCAM-directed PROBODY antibody–drug conjugate, in patients with heavily pretreated metastatic colorectal cancer. In the dose-expansion cohorts, the confirmed overall response rate (ORR) reached 32% at the 10 mg/kg dose and 20% at 8.6 mg/kg, with a disease control rate of 88% across all expansion levels. Median PFSwas estimated at approximately 7 months, a notable signal in this late-line setting. The safety profile remained manageable; treatment-related adverse events were primarily grade 1 or 2, with diarrhea being most common. Based on these results, registrational study discussions with the FDA are planned for mid-2026.

FDA Confirms Potential Accelerated Path for Givastomig in GE Cancer

The FDA has confirmed that the investigational bispecific antibody givastomig (TJ033721/ABL111) is eligible for an accelerated approval pathway for the first-line treatment of HER2-negative, CLDN18.2-positive, and PD-L1–positive gastric and gastroesophageal junction cancers. This decision follows a productive Type B meeting and is supported by phase 1b data showing a 75% ORRand a median PFSof 16.9 months when combined with nivolumab and chemotherapy.

Givastomig targets both CLDN18.2 and 4-1BB, a design intended to concentrate T-cell activation within the tumor microenvironment while minimizing systemic toxicity. Based on these promising efficacy and safety results, a registrational phase 3 trial is expected to initiate in late 2026, using ORRas the primary end point to support accelerated approval.