CAR-T in RCC – Ambitious, But Toxic
“Phase 1 CART therapy in RCC (n=48). Treatment with ALLO-316 (anti-CD70). Quite significant tox as expected with CRS and autoimmune tox etc. RRs of 26% with short follow up in heavily pretreated patients. Cure/deep response should be the ambition”
Casdatifan + Cabo Combo Shows Promise
“Phase 1 of casdatifan (HIF2a) + cabozantinib (VEGF TKI) in ccRCC (n=27 short follow up). Most patients had no prior VEGF. Well tolerated with anaemia + fatigue main TRAEs. RRs of over 40% leading to the PEAK1 trial of Cabo/casdatifan vs Cabo in pretreated M1 RCC”
9-Year Data from Ipi/Nivo: Deep, Durable Benefit
“Final ipi/nivo data – 9.3 yrs follow up – like the Voyager space probe travelling beyond Pluto. OS HR of 0.69 & 0.80 in int/poor risk & good risk disease. 9 yr OS = 30% vs 20% in ITT. Early immune therapy saves lives. IMDC seems irrelevant in picking patients for IO”
Sequencing SG + Avelumab in Urothelial Cancer: A Cautionary Tale
“RII of SG + avelumab sequenced post platinum chemo in UC = Increased PFS without OS (HR = 0.49 / 0.79). Vinflunine had similar data in a similar trial before IO. Maximising PFS requires longer cytotoxic duration, but without OS & with better alternatives (EVP) suspect this won’t progress”
ADC + IO: Nectin4 + Toripalimab Excite
“Interim analysis for 9MW2821 (Nectin4/MMAE ADC) & Toripalimab (n=40) RR = 80%. PFS = 1 year. Small numbers and short follow up but it looks a bit like EVP, with slightly different toxicity. Randomised phase 3 announced in China.
“Impressive data for 9MW2821 (Nectin4/MMAE ADC) & Toripalimab (n=40) RR = 80% (EVP & DVP 73% / 75% in phase 2). TRAEs >G3 neutrophil ↓ (8%), rash (5%), ALT↑ (5%). Less skin tox? Also high responses in Nectin4 low. This will be in R3 very soon in China I suspect.”
Neoadjuvant ADC + IO in MIBC: A Step Forward
“SURE-02: A phase 2 of neoadjuvant SG (TROP2 ADC) + Pembro (n=31). Primary endpoint = clinical CR (MRI and cystoscopy). cCR = 44%, 12% G3 or more TRAEs. More cCR data as an endpoint needed. pCR for durvalumab NAC = 37%. Heterogeneity in MIBC endpoints makes assessment tricky”
CLONEVO: Biomarker-Rich Trial in Cisplatin-Ineligible MIBC
“CLONEVO: Preoperative abemaciclib (CDK4/6 inhibitor) in cisplatin ineligible MIBC (n=20) pCR = 18% seems modest. RB1 phosphorylation confirmed on-target activity. Serial ctDNA showed 27% ↓ in TF. Great biomarker work showing suppression of E2F-dependent cell proliferation”
STELLAR 002: LAG3 Disappoints Again
“In STELLAR 002 zanzalintinib nivolumab +/- rela (LAG3) demonstrated promising preliminary clinical activity for the doublet without clear benefit associated with adding LAG3. Triplets and targets beyond PD1 abs LAG3 both appear challenging as with COSMIC313”
Adjuvant Pembro in RCC: 5-Year Update
“The 5 yr follow up for adjuvant pembro in RCC (KN564): continued benefit – DFS (5 yr 52% vs 61% – HR 0.71) OS (5 yr 82% vs 88% HR 0.66). Maintained KM curve separation. No subgroup stands out. 18% TRAEs. Long term tox difficult to quantify but benefits seem to outweigh risks”
NMIBC: A Sea of Options, But No Head-to-Head
“Different novel therapies in NMIBC are approved. Most are being tested in BCG pretreated patients. All have activity & many have a favourite, but with small single arm trials no one knows which is best. Now there are choices we should randomise?”
