OPTIMUM: A randomized phase 2 study of maintenance olaparib (Ola) with or without durvalumab (Durva) in DDR gene-mutated advanced biliary tract cancer (aBTC)

OPTIMUM

Patient / Population Intervention / Exposure Comparison Outcome

In patients with DDR gene-mutated advanced biliary tract cancer without progression on first-line platinum-based therapy, maintenance olaparib with or without durvalumab achieved a 6-month progression-free survival rate of 62.3% in the full analysis set, above the historical 48.0% used to power the trial.

N

63patients

Design

Randomised, open-label, non-comparative phase 2 trial in patients with advanced biliary tract cancer, ECOG PS 0-1, at least one predefined somatic or germline DDR gene mutation and no disease progression after at least 16 weeks of first-line platinum-based therapy, randomised 1:1 to maintenance olaparib plus durvalumab or olaparib alone (NCT05222971).

Endpoint

6-month progression-free survival rate in the Full Analysis Set, tested against a historical rate of 48.0%.

Result6-month PFS rate in the Full Analysis Set 62.3% (51.2-71.5) overall, 62.5% (95% CI 46.8-74.7) with olaparib plus durvalumab and 62.1% (45.5-74.9) with olaparib alone. Median PFS 8.2 months overall (90% CI 6.8-11.1), 7.7 vs 8.2 months. 1-year PFS 37.2% overall, 31.7% vs 41.1%. Median OS 18.9 months overall, 16.5 vs 29.6 months. 2-year OS 40.1% (28.0-51.9) overall, 25.0% vs 53.6%. ORR 27.5% overall, 30.0% vs 25.0%. In the core homologous recombination deficiency group (n=18, 30%), median PFS was 20.5 vs 7.4 months (P=0.008) and median OS not reached vs 16.5 months (P=0.007) compared with other patients. Higher ctDNA VAF at the start of study treatment correlated negatively with PFS and OS. No new safety profile was seen with olaparib with or without durvalumab.

Yoo C, Jeong H, Oh J, et al. Presented at ESMO Congress 2026, abstract LBA22, 26 October. Not yet published.

Discussion & critique

In the Full Analysis Set the pooled 6-month PFS rate was 62.3%, and its interval lies wholly above the historical 48.0%, although the abstract does not explicitly say whether the primary endpoint was met. The trial is non-comparative and open label with about 30 patients per arm, so it cannot formally show whether durvalumab adds anything. The arms had near-identical 6-month PFS and numerically lower overall survival with the combination, but these differences are untested. The benefit in the core HRD group comes from a subgroup of 18 patients compared with the rest, not from randomisation, and the abstract gives no figures for adverse events.