David H Aggen, MD PhD

Out now in @ClinCancerRes: targeting the AHR pathway to overcome intratumoral immune resistance in bladder cancer tinyurl.com/39td758b 🚨We shouldn't give up on I/O in the treatment refractory setting in metastatic UC. As EV/P and DV ± T move earlier in metastatic UC, later-line sequencing is the new challenge — overlapping toxicities (neuropathy, cytopenias, rash) often limit “what’s next?” Tremendous effort from @MeredithMcKean @JCensits @OAlhalabiMD @abowmanmd @alantanmd @jasonlukemd A tweetorial 1/6

#GUPath Poster Walk#1 with @h_alahmadie #USCAP2026

pCR after neoadjuvant chemotherapy has long been considered a strong prognostic marker. But adding ultra-sensitive ctDNA changes the picture. In the PREDICT-DNA trial (NeXT Personal @PersonalisInc ), ctDNA-negative patients among non-pCR cases showed outcomes comparable to pCR. @JCO_ASCO Small sample size—but a highly impactful finding. ascopubs.org/doi/10.1200/JC…

Over expression of efflux pump ABCC1 as mechanism of resistance to ADCs with a TOP1i payload.

Enjoying a Saturday at #NYGU #GOTOPER with @DSolit reviewing ADC target expression in variant histology bladder cancer. Fantastic work in collaboration with @h_alahmadie #GU #NYGU26

My laboratory is seeking a computational biologist postdoc to join our team and lead integrative analyses supporting several newly funded and pending research programs focused on tumor immunology and antibody-based immunotherapy.

Thanks to all our TeamHOPP riders over the past 15 years. From one bike in 2012 to 51 bikes as part of 18 rides in 8 cities in 2026. Powering cures through science. 20 years closer to a cure. As Barb keeps telling me - Let's Get it Done!!!! @Cycle4Survival

*Nectin-4! Autocorrect failure I thought my phone had learned it by now

Very proud of @MichalSternsch and her on-going work to unravel newton-4 biology in the context of EV/P. Here she shows that nectin-4 localization matters in the context of EV/P #ASCOGU26 #GU26

#ASCOGU26 🧵2/2 RCC: LITESPARK-011 — Belzutifan+lenvatinib vs cabozantinib in advanced ccRCC post anti-PD-(L)1. -mPFS 14.8 vs 10.7 mo (HR 0.70), -DoR nearly doubled (23.0 vs 12.3 mo), significant ORR improvement. First phase 3 regimen to beat cabo in post-IO RCC. OS trending positive, awaiting maturation.

#ASCOGU26 1/2 RCC: LITESPARK-022 — Adjuvant belzutifan+pembro vs pembro alone in post-nephrectomy high-risk ccRCC (N=1,841). - 28% reduction in risk of recurrence/death. -~81% cancer-free vs 74% at median 28.4 mo. First combo to beat pembro monotherapy in the adjuvant kidney cancer setting for DFS and OS still maturing.

#ASCOGU26 🧵5/5: Novel targets expanding the UC toolkit. - FX-909 (first-in-class PPARγ inhibitor) showing early signal in luminal/PPARG-high advanced UC — first agent targeting the transcriptional driver of luminal lineage. - Sac-TMT (TROP2 ADC) + pembro also entering the space. Biomarker-driven tx diversifying fast.

#ASCOGU26 🧵4/5: RC48G001 — disitamab vedotin (HER2-directed ADC) ± pembro in HER2-expressing la/mUC. Activity noted in HER2 1+ and 2+ tumors in advanced UC. Relevant as we learn more about HER2/Nectin-4 co-expression patterns and optimal ADC target selection. See our abstract for HER2 / Nectin-4 Co-expression in metastatic bladder cancer.

#ASCOGU26 🧵3/5: NIAGARA utDNA data — first-ever utDNA with clinical correlation in a phase 3 periop trial. - Combined utDNA+ctDNA post-neoadjuvant/pre-cystectomy identified the highest 24-mo EFS group. - utDNA tracks residual non-invasive disease; ctDNA tracks invasive disease.

#ASCOGU26 🧵2/5: KEYNOTE-905 update in cis-INELIGIBLE MIBC reinforces the story. Periop EV+pembro: - pCR 57.1% vs 8.6%, - pDS 65.9% vs 12.6% vs surgery alone. Now FDA-approved. EV+pembro is the periop standard regardless of cisplatin fitness.

UC Takeaways from #ASCOGU26 1) KEYNOTE-B15 is a landmark. Periop EV+pembro vs gem/cis in cis-eligible MIBC: EFS HR 0.53, pCR 55.8% vs 32.5%, OS benefit. First regimen to displace cisplatin in curative-intent bladder cancer in ~25 yrs.

FIH PPARG inverse agonist for luminal urothelial cancer rdcu.be/e5602 #GU26 @NatureMedicine @TischCancer @apolo_andrea @shilpaonc @BourlonMaite @PGrivasMDPhD @AmandaNizamMD @DrKarineTawagi @drenriquegrande @PGrivasMDPhD @urotoday @Uromigos @OncBrothers @OncoAlert

Biomarker insights by @MichvdHeijden: NIAGARA utDNA/ctDNA baseline low utDNA → better EFS (HR 0.65). utDNA+ rate decreased 85%→55% to pre-RC utDNA clearance → longer EFS (HR 0.24). Pre-RC utDNA- tracks pCR (72% vs 18%). #GU26 #BladderCancer @OncoAlert @OncBrothers

Disitimab Vedotin (HER2/MMAE ADC) was tested in HER2-positive (n=73, RR 55%) and HER2-low (n=78, RR 53%) pretreated advanced bladder cancer outside of China. No clear efficacy difference according to HER status(PFS 6 months and OS 17-20 mnths). Only about 20% of UC patients are HER2 negative. Cumulative neuropathy is like EV, but perhaps less skin rash. It doesn’t have any clear advantages over EV. Sequencing data with EV suggests a lack of complete cross resistant - more date needed). The randomised phase 3 DVP vs. Chemo 1st line trial is complete. #GU26

3 studies testing Perioperative immune bases therapy (EVP or Gem/Cis/Durva) in muscle invasive bladder all have shown an OS advantage vs standard of care. KN905 (EVP) is distinct in that it’s in a cisplatin ineligible population (accounting for the poor performance of the control arm). It’s also a smaller trial. The control arm of KN-B15 performed slightly better than NIAGARA (Gem/cis for both), but the trials are otherwise similar. The pCR in the EVP trails and the consistent efficacy of EVP is striking. #GU26

The standard of care for MIBC will now include perioperative EVP for both cisplatin eligible and ineligible #BladderCancer pts. The EV304 study presented today @MattGalsky shows an improvement in EFS (HR 0.53) and OS (HR 0.65) for EVP over GC. @ASCO #GU26