Kyle Doherty

Key Takeaways Baseline ctDNA positivity stratified a very high-risk group, with 24-month DFS falling to 38.8% (pembro) and 18.3% (placebo) by 64-plex. Low assay sensitivity (10%–15%) despite high specificity (≈98%–99%) undermined baseline exome-based ctDNA as a standalone MRD tool in this setting. Pembrolizumab improved DFS versus placebo regardless of baseline ctDNA, with ctDNA-negative HR 0.78 and ctDNA-positive HR ~0.68 (64-plex) though imprecise. Tumor-informed Signatera exome-based testing used 64-plex as primary, with 16-plex simulated, in a treated cohort with available tissue, blood, and plasma specimens. On-treatment ctDNA clearance by cycle 5 day 1 was numerically higher with pembrolizumab than placebo (e.g., 55.6% vs 36.0% with 64-plex). SHOW MORE

Key Takeaways FDA expanded adjuvant options in resected intermediate-high/high-risk ccRCC by authorizing belzutifan with pembrolizumab after nephrectomy, including post-metastasectomy settings. LITESPARK-022 showed a statistically significant DFS improvement for belzutifan plus pembrolizumab versus pembrolizumab (HR 0.72; 95% CI, 0.59–0.87), with medians not reached. Overall survival results remained immature at the pre-specified interim analysis, limiting definitive conclusions on long-term survival benefit. Combination therapy increased adverse-event burden versus monotherapy, including grade ≥3 TEAEs (52.1% vs 30.2%) and serious TEAEs (29.5% vs 19.9%). Immune-mediated AEs/infusion reactions were comparable between arms, while treatment-related grade ≥3 events were higher with the combination (42.2% vs 17.9%). SHOW MORE

Key Takeaways A 3+3 phase 1b escalated cadonilimab 10 or 15 mg/kg q3w with axitinib 5 mg BID, selecting 10 mg/kg q3w as RP2D. Confirmed ORR was 51.6% and DCR 96.8% in phase 2, with median PFS 14.2 months and median DOR 17.5 months. Transaminase elevations, hypertriglyceridemia, proteinuria, diarrhea, and hypertension were common; grade ≥3 TRAEs occurred in 59.5%, and treatment interruptions were frequent, yet permanent discontinuations were rare. Histology influenced benefit, with FH-dRCC ORR 81.8% and no responses in collecting duct carcinoma; liver metastases showed ORR 87.5%, and synchronous disease had shorter PFS. SHOW MORE

Key Takeaways From the Subgroup Analyses of PSMAddition Adding lutetium Lu 177 vipivotide tetraxetan to an ADT/ARPI improved rPFS across

Key Takeaways First-line zongertinib achieved a 76% ORR with median PFS 14.4 months and DOR 15.2 months, supporting its February 2026 accelerated approval for HER2 TKD–mutant NSCLC. Sevabertinib produced a 75.3% ORR and median PFS 13.5 months in SOHO-01 cohort F, prompting FDA priority review for first-line use in HER2 TKD–activating mutations. Zongertinib demonstrated intracranial activity in baseline active brain metastases (47% intracranial ORR), although CNS DOR/PFS appeared shorter than extracranial control in small cohorts. In previously treated HER2 TKD–mutant NSCLC, zongertinib (71% ORR; PFS 12.4 months) and sevabertinib (66.7% ORR; PFS 8.3 months) are FDA-approved options. Treatment choice often hinges on AE profiles and logistics: zongertinib is viewed as “cleaner,” while sevabertinib's EGFR coverage may add rash/diarrhea yet potentially affect resistance pathways. SHOW MORE

External validation of a circulating immune protein signature model confirmed its prognostic value for OS in recurrent ovarian cancer.

Key Takeaways Zongertinib demonstrated high activity in HER2 TKD–mutated disease (ORR 71%, median PFS 12.4 months) with reduced efficacy in non-TKD mutations (ORR 30%) and preserved activity post–HER2 ADC exposure (ORR 48%). Sevabertinib produced ORR 66.7% and median PFS 8.3 months in HER2-targeted therapy–naïve, pretreated HER2-mutant NSCLC, with median DOR 9.5 months at 19.5-month follow-up. Trastuzumab deruxtecan at 5.4 mg/kg achieved ORR 50% with median PFS 10.0 months, median DOR 12.6 months, and median OS 19.0 months in HER2-mutant metastatic NSCLC. Sequencing discussions emphasized starting a tolerable HER2 TKI (often zongertinib), citing ILD as potentially treatment-ending in lung cancer and viewing modest ORR differences as less decisive clinically. CNS disease and patient priorities influenced choice, with a preference for TKIs in brain metastases and recognition that ADC-associated alopecia can meaningfully affect patient acceptance despite preserved efficacy. SHOW MORE

Key Takeaways Regulatory filing seeks approval of subcutaneous mosunetuzumab plus IV polatuzumab vedotin for adult R/R LBCL after ≥1 prior line, with FDA decision expected February 9, 2027. SUNMO randomized transplant-ineligible R/R LBCL patients 2:1 to Mosun-Pola (8 and 6 cycles, 21-day) versus R-GemOx (8 cycles, 14–21-day), stratified by lines and relapse status. IRC-assessed median PFS improved to 11.6 vs 3.8 months (HR, 0.41), with 2-year PFS 37.5% vs 14.3%, favoring Mosun-Pola. Response outcomes favored Mosun-Pola: ORR 70.3% vs 40.0%, CR 51.4% vs 24.3%, median DOR 18.8 vs 6.0 months, and stronger 2-year DOR/CR durability. CRS occurred in 25.9% (mostly grade 1–2; grade 3, 0.7%), with serious CRS 5.2%, median onset 3 days and duration 3 days, consistent with known safety. SHOW MORE

Neoadjuvant nivolumab yielded a 68.2% clinical complete response rate in patients with resectable mismatch repair–deficient endometrial cancer.

The NCCN has included tumor-informed multiplex PCR ctDNA-MRD testing in the treatment approach for patients with MIBC.