The Targeted Pulse: FDA Approvals, Trial Updates, and ASH 2025 Previews

Welcome to this week's edition of The Targeted Pulse, your weekly wrap-up of the top developments in oncology. This week, we saw FDA decisions, learned about care-changing trial data, and got a preview of the most anticipated 67th American Society of Hematology (ASH) Annual Meeting and Expositionabstracts. From regulatory designations for promising new drugs to crucial clinical trials, here are the top stories that shaped the week.

FDA Approves Novel Blood-Based Assay to Stratify Prostate Cancer Biopsy Risk

The FDA has granted premarket approval to the IsoPSA blood-based in vitro diagnostic kit, intended to aid clinicians in deciding whether to proceed with prostate biopsy. It is indicated for men aged ≥ 50 years with elevated prostate-specific antigen (PSA) levels.

Unlike traditional PSA testing, IsoPSA leverages the IsoClear™ platform to analyze structural characteristics (isoforms) of the PSA protein, offering enhanced specificity. Clinical utility is recognized by inclusion in NCCN and AUA/SUO guidelines, as it improves risk stratification for high-grade (Gleason score ≥7) prostate cancer. The test is expected to decrease unnecessary biopsies stemming from benign PSA elevations.

Sacituzumab Tirumotecan Plus Pembrolizumab Improves PFS in NSCLC

The phase 3 OptiTROP-Lung05 trial demonstrated that the combination of sacituzumab tirumotecan (sac-TMT), a TROP2-directed antibody-drug conjugate [ADC], plus pembrolizumab (Keytruda) offers a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with pembrolizumab monotherapy for first-line treatment of advanced, PD-L1-positive non–small cell lung cancer (NSCLC).

This study marks the first time an ADC combined with an immune checkpoint inhibitor has met a primary end point in the first-line NSCLC setting. The regimen also showed a positive trend in overall survival (OS) with a manageable safety profile. This combination represents a new, highly effective, and novel therapeutic option for clinicians managing these patients.

FDA Grants Traditional Approval to Pirtobrutinib in CLL/SLL

The FDA has granted traditional approval to pirtobrutinib (Jaypirca), a highly selective, noncovalent Bruton's tyrosine kinase (BTK) inhibitor, for adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This indication specifically targets patients previously treated with a covalent BTK inhibitor.

The decision is based on the phase 3 BRUIN-CLL-321 trial, which showed a statistically and clinically significant PFS benefit. Median PFS was 11.2 months (95% CI, 9.5–11.4) with pirtobrutinib vs 8.7 months (95% CI, 7.2–10.2) for investigator's choice of therapy (HR, 0.58; P =.0105). This noncovalent agent provides a mechanism to continue BTK pathway targeting after resistance to covalent inhibitors.

Poll: Vote on the Top Abstracts to Watch at ASH 2025

The Targeted Oncology® poll highlighted several practice-changing abstracts for the 67th ASH Annual Meeting and Exposition, primarily in multiple myeloma (MM), CLL, and myelofibrosis. The most anticipated presentation is the phase 3 MajesTEC-3 trial, which evaluated the combination of the bispecific antibody teclistamab plus daratumumab (Tec-Dara) against standard-of-care regimens in relapsed/refractory MM. The data demonstrated statistically and clinically significant improvements in PFS and OS for Tec-Dara. These findings support establishing the Tec-Dara regimen as a new standard of care early in the R/R MM treatment landscape. Other highly anticipated data include primary results for pirtobrutinib in previously untreated CLL/SLL (LBA-3).

New-Generation ADC Elicits Responses in Neoadjuvant HER2+ Breast Cancer

The bispecific HER2-directed ADC TQB2102 demonstrated robust activity in the phase 2 TQB2102-II-01 trial as a neoadjuvant therapy for HER2-positive breast cancer. Its novel design targets 2 non-overlapping HER2 epitopes to enhance blockade.

The 6.0 mg/kg regimen administered over 8 cycles achieved the highest total pathologic complete response rate at 76.9% (90% CI, 62.3%–87.6%). The drug exhibited a favorable safety profile, with grade 3 treatment-related adverse events occurring in 27.9% of patients across all cohorts. These compelling efficacy and safety data support the ongoing randomized phase 3 evaluation of TQB2102 against standard neoadjuvant regimens in this patient population.