Imfinzi squares up to Keytruda with a Padcev combo

AstraZeneca has followed Imfinzi’s success in perioperative muscle-invasive bladder cancer, where the drug was approved for cisplatin-eligible patients a year ago, with a win in the Volga study, which tested it with Padcev in the cisplatin-ineligible setting.This could help the company catch up with Pfizer/Merck & Co, whose Padcev/Keytruda combo has been available for cisplatin-ineligible patients since last November. And, in the cisplatin-eligible setting of Astra’s Niagara trial, Imfinzi remains ahead for now: Merck quietly slipped out the failure of Keytruda’s analogous Keynote-866 study last month.Still, Astra’s advantage might not last long. Merck/Pfizer detailed a win in Keynote-B15, a Keytruda/Padcev study in cisplatin-eligible MIBC, at the ASCO-GU meeting in February. This now faces an FDA action date of 17 August, and if approved would mark the first such success for a chemo-free regimen in these MIBC patients.Accordingly, Merck’s failure in Keynote-866 might not matter much. A third player, Bristol Myers Squibb, was testing Opdivo plus chemo in a similarly designed trial coded CA017-078, which was supposed to have read out in the first half of this year; however, last month Bristol said it was discontinuing development of Opdivo in periadjuvant MIBC. Selected phase 3 studies in cisplatin-eligible MIBCDrugCompanyTrialSettingStatusImfinzi + gem/cisAstraZenecaNiagaraAdj & neoadjApproved Mar 2025Keytruda + PadcevMerck & Co/ PfizerKeynote-B15Adj & neoadjFiled, 17 Aug PDUFA dateKeytruda + gem/cisMerck & CoKeynote-866Adj & neoadjFailed Apr 2026Opdivo + gem/cisBristol Myers SquibbCA017-078Adj & neoadjFailed Apr 2026Note: gem/cis=gemcitabine + cisplatin. Source: OncologyPipeline. Meanwhile, in cisplatin-ineligible MIBC, Astra on Thursday said the Volga study had shown an Imfinzi/Padcev doublet to beat surgery alone, with statistically significant and clinically meaningful improvements in the primary endpoint of event-free survival – as well as in the key secondary of overall survival.That could put the combo in line with Keytruda/Padcev in this setting, though until the full Volga data are published Astra’s results can’t be held up directly against Merck/Pfizer’s success in Keynote-905. In Keynote-905 the Padcev combo beat surgery alone with a 0.40 hazard ratio for EFS, while risk of death was cut by 50% (p<0.001).One curious fact about Volga is that trial’s second active cohort, which added Imjudo on top of Imfinzi/Padcev. Astra said the triplet hit on EFS at this interim analysis, but the OS data were not statistically significant, and would be formally reassessed later. It’s not clear why adding Imjudo, an anti-CTLA-4 MAb, appears to be causing patients to do worse, but toxicity is one possibility.And Roche?Wile cisplatin-eligible MIBC is a two-horse battle, in cisplatin-ineligibles there’s a third contender, Roche’s Tecentriq, which faces an imminent FDA decision on its approvability on the basis of the Imvigor-011 study.However, here the Swiss group has taken a somewhat different approach, firstly by designing Imvigor-011 as a trial only in the adjuvant setting, rather than the periadjuvant designs of Volga and Keynote-905, where the various combos are given before as well as after bladder resection.Most importantly, Imvigor-011 is an attempt at changing treatment practice by introducing testing for circulating tumour DNA (ctDNA) as a means for deciding whether Tecentriq should be administered. Imvigor-011 data at last year’s ESMO showed Tecentriq in this ctDNA-guided setting to cut risk of death by 41%, and the risk of disease recurrence or death by 36%, versus placebo.Roche says using ctDNA testing this way could spare people at low risk of recurrence from unnecessary treatment. It’s curious that the FDA hasn’t convened an advisory committee to discuss this filing, as it did for the ctDNA-guided practice-changing approach of the Serena-6 breast cancer trial of Astra’s camizestrant. Selected phase 3 studies in cisplatin-ineligible or refusing MIBCDrugCompanyTrialSettingStatusKeytruda + PadcevMerck & Co/ PfizerKeynote-905Adj & neoadjApproved Nov 2025TecentriqRocheImvigor-011Adj only, ctDNA+veFiled, May 2026 PDUFA dateImfinzi + Padcev +/- ImjudoAstraZeneca/ PfizerVolgaAdj & neoadjToplined +ve for Padcev doubletSource: OncologyPipeline.