Inavolisib for HER2-positive breast cancer (INAVO122)

Resolution Criteria Trial: NCT05894239 Selected endpoint key: 7a371d5418f6aedb32a53f5bf23b125061aaf6a7a9168adda93a687da0f6578b Selected endpoint: Investigator-Assessed Progression-Free Survival (PFS) Endpoint type: PFS Protocol outcome group: primary Endpoint description: Not provided by ClinicalTrials.gov. Endpoint timeframe: Up to approximately 40 months ClinicalTrials.gov population: Randomized participants with centrally confirmed PIK3CA-mutated, HER2-positive, unresectable locally advanced or metastatic breast cancer who completed first-line induction therapy with a taxane plus pertuzumab and trastuzumab/Phesgo and met the protocol eligibility criteria. Market population: Randomized participants with centrally confirmed PIK3CA-mutated, HER2-positive, unresectable locally advanced or metastatic breast cancer who completed first-line induction therapy with a taxane plus pertuzumab and trastuzumab/Phesgo and met the protocol eligibility criteria. Analysis set: The enumerated ClinicalTrials.gov outcome and official Roche study poster do not specify a named analysis-set label; the primary comparison is between the two 1:1 randomized maintenance-treatment arms. Comparison: Maintenance inavolisib 9 mg orally once daily plus Phesgo every 3 weeks versus maintenance placebo orally once daily plus Phesgo every 3 weeks after first-line induction therapy; concomitant endocrine therapy during maintenance is allowed at the physician's discretion in either arm. Success direction: lower Success rule: Success requires a statistically significant improvement in investigator-assessed progression-free survival for inavolisib plus Phesgo versus placebo plus Phesgo. PFS is measured from randomization to the first occurrence of disease progression under RECIST v1.1 or death from any cause, whichever occurs first, through approximately 40 months. The primary analysis uses a two-sided stratified log-rank test at a two-sided 5% significance level; therefore, the prespecified statistical success criterion must be met with the treatment effect favoring inavolisib plus Phesgo. A stratified Cox model estimates the hazard ratio and 95% confidence interval. ClinicalTrials.gov source: https://clinicaltrials.gov/study/NCT05894239?tab=researcher#outcome-measures:~:text=Investigator-Assessed%20Progression-Free%20Survival%20(PFS) YES 1. The exact selected endpoint (Investigator-Assessed Progression-Free Survival (PFS)) satisfies the approved success rule in the specified population, analysis set, comparison, and timepoint. 2. The result is supported by a qualifying source in the approved evidence hierarchy. NO 1. The exact selected endpoint (Investigator-Assessed Progression-Free Survival (PFS)) misses its approved success rule. 2. No qualifying disclosure of the selected endpoint is available by 2027-12-31 at 23:59:59 UTC. NO DECISION / ADMIN REVIEW 1. Available evidence is contradictory, incomplete, pooled, interim, subgroup-only, or does not match the approved population, analysis set, comparison, and timepoint. Resolution deadline: 2027-12-31T23:59:59Z Deadline evidence: Admin-verified bounded deadline: Roche Pharma Day, September 28, 2026, page 45 lists Phase III INAVO122 clinical results in its 2027 key newsflow outlook, and page 124 explicitly states INAVO122 Readout 2027. The market deadline is the conservative final day of the disclosed year, 2027-12-31. Roche notes that outcome studies are event-driven and timelines may change. The registry primary-completion estimate is not treated as the disclosure date. Deadline evidence source: https://assets.roche.com/f/176343/x/51deda2587/20260928_final_pharma-day-2026-publish-1.pdf Evidence precedence 1. ClinicalTrials.gov posted results 2. Sponsor regulatory filing or official release 3. Peer-reviewed publication or official conference abstract Only the selected endpoint in the specified population, analysis set, comparison, and timeframe can resolve YES. Overall positive messaging, another endpoint, interim results, pooled analyses, or an unmatched subgroup cannot resolve YES.