ESMO 2024 ran from Sept 13-17 in Barcelona, Spain, where the top oncology players came together to share the latest data across tumor types and MOAs. Below, Adelphi explores select hot topics, including ADCs in bladder cancer, TIGITs and bispecific antibodies, and Keytruda in gynecological cancer.
ADCs in Bladder Cancer
Preliminary efficacy and safety data for disitamab vedotin (Pfizer) combined with pembrolizumab (Keytruda) was presented at ESMO. The positive data showed encouraging results consistent with previously presented data in treatment-naïve patients with HER2-expressing locally advanced or metastatic urothelial carcinoma (mUC). Data showed a response in both HER2-positive and HER2-low mUC. A Ph3 study is currently exploring the efficacy and safety of the combination in 1L with chemotherapy.
Pfizer also presented additional analysis from EV-302 showing positive results for enfortumab vedotin (Padcev) + pembrolizumab (Keytruda) in mUC, a hot topic from last year’s conference. The data demonstrated consistent PFS, OS, and ORR vs. chemotherapy, regardless of Nectin-4 or PD-L1 expression.
TIGITs and Bispecific Antibodies
GSK and iTeos Therapeutics shared the highlights of their Ph2 TIGIT trial at ESMO 2024. Results of the trial showed that a combination of belrestotug, an anti-TIGIT antibody, and Jemperli (dostarlimab) increased ORR by more than 30% compared to monotherapy in NSCLC. Despite the strong efficacy data, it appeared that investors may have been overly alarmed by the toxicity signals, which GSK and iTeos indicated could be corrected with a change in protocol (increasing access to labs to screen for risk factors for immune-mediated myocarditis, thus reducing discontinuations). However, investors still seemed concerned, causing iTeos stock to drop by nearly 30%.
In other impressive news, Jazz shared Ph2 data for their HER2 bispecific antibody (zanidatamab), showing 59% survival at 30 months and a cORR of 84% in metastatic gastro esophageal cancer (mGEA). Jazz touted the potential for zanidatamab to address a significant unmet need in mGEA, noting there were no treatment-related deaths in the 30-month data and discontinuations were low. A Ph3 trial is currently enrolling, with results expected in mid-2025.
Gynecological Cancer
Merck presented data backing their phase 3 KN-A18 (approved in Jan 2024) study combining pembrolizumab (Keytruda) + concurrent chemoradiotherapy (CCRT) in patients with previously untreated locally advanced cervical cancer (LACC). Patients treated with this combination showed one-third lower risk for disease progression than those who were treated with CCRT alone. Merck’s KN-A18 demonstrated significant and clinically meaningful improvement in PFS and OS, establishing Keytruda + CCRT as a strong contender for the next standard of care in LACC.
Besides the KN-A18 data, Merck presented a number of other studies in gynecological cancer, with mixed results. Merck reported in May that Keytruda failed to make a statistically significant impact on DFS in newly diagnosed, high-risk endometrial cancer, with events being equal between the Keytruda and control arm. However, a subgroup analysis showed that Keytruda did make a clinically meaningful DFS improvement in patients with dMMR (mismatch repair deficient) tumors. This data suggests that Keytruda might be a strong option in those who are biomarker tested.