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Indication: IMFINZI in combination with gemcitabine and cisplatin is indicated for the first line treatment of adults with locally advanced, unresectable or metastatic BTC.1
685 patients with advanced BTC were recruited from 17 countries2
A Phase III, randomised, double-blind, placebo-controlled, global, multicentre study evaluating IMFINZI + Gem-Cis vs. placebo + Gem-Cis in 1L unresectable BTC3,4
Patients randomised in China after last patient randomised in the global cohort, will only be analysed in the China Cohort (n=130).
*Cisplatin (25 mg/m2) and gemcitabine (1000 mg/m2) administered on Days 1 and 8 of each cycle Q3W, for up to 8 cycles (SoC chemotherapy).
Baseline characteristics in the overall population of TOPAZ-14,5
| IMFINZI + Gem-Cis
(n=341) | Placebo + Gem-Cis
(n=344) | ||
| Age (years) | Median, (min, max) | 64.0 (20, 84) | 64.0 (31, 85) |
| Gender | Male, n (%) | 169 (49.6) | 176 (51.2) |
| Region | Asia, n (%) Rest of world,2 n (%) Europe North America South America | 178 (52.2) 163 (47.8) 108 (31.7) 37 (10.9) 18 (5.3) | 196 (57.0) 148 (43.0) 107 (31.1) 28 (8.1) 13 (3.8) |
| ECOG PS | 0, n (%) 1, n (%) | 173 (50.7) 168 (49.3) | 163 (47.4) 181 (52.6) |
| Disease classification | Locally advanced, n (%) Metastasis, n (%) | 38 (11.1) 303 (88.9) | 57 (16.6) 286 (83.1) |
| Disease status | Initially unresectable, n (%) Recurrent, n (%) | 274 (80.4) 67 (19.6) | 279 (81.1) 64 (18.6) |
| Primary tumour location | iCCA, n (%) eCCA, n (%) GBC, n (%) | 190 (55.7) 66 (19.4) 85 (24.9) | 193 (56.1) 65 (18.9) 86 (25.0) |
| PD-L1 expression | Positive (TIP≥1%), n (%) Negative (TIP<1%), n (%) Missing, n (%) | 197 (57.8) 103 (30.2) 41 (12.0) | 205 (59.6) 103 (29.9) 36 (10.5) |
| Virology status | Any viral hepatitis B, n (%) Prior hepatitis C, n (%) | 69 (20.2) 8 (2.3) | 81 (23.5) 10 (2.9) |
1L, first line; aBTC, advanced biliary tract cancer; ADA, antidrug antibody; AVC, ampulla of Vater carcinoma; BTC, biliary tract cancer; DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; eCCA, extrahepatic cholangiocarcinoma; GBC, gallbladder cancer; Gem-Cis, gemcitabine-cisplatin; iCCA, intrahepatic cholangiocarcinoma; IV, intravenous; ORR, objective response rate; OS, overall survival; PD, progressive disease; PD-L1, programmed cell death-ligand 1; PFS, progression-free survival; PK, pharmacokinetic; PRO, patient-reported outcome; PS, performance status; Q3W, dose every 3 weeks; Q4W, dose every 4 weeks; R, randomisation; RECIST, Response Evaluation Criteria in Solid Tumours; SoC, standard of care; TIP, tumour/immune cell positivity; ULN, upper limit of normal.
IMFINZI + Gem-Cis
(n=341, 95% Cl 18.7–28.9)
Placebo + Gem-Cis
(n=344, 95% Cl 7.6–16.2)
(Data cut-off: February, 2022)
12.9 Months (11.6–14.1)
IMFINZI + Gem-Cis
11.3 Months (10.1–12.5)
Placebo + Gem-Cis
Adapted from Oh D-Y et al. Poster presentation. 2022
*The analysis for HR was performed using a stratified Cox proportional hazards model, and 2-sided p-value is based on a stratified log-rank test. Both are adjusted for disease status and primary tumour location.2
†At the time of the updated analysis (data cut-off: February 25, 2022), 527 events (77% OS maturity) had occurred: 248 patients (73%) with IMINZI + Gem-Cis and 279 (81%) with Placebo + Gem-Cis. OS was not formally tested for statistical significance at this time. OS at 24 months was estimated (Using Kaplan-Meier curve) and presented by treatment arm.2
‡IMFINZI + Gem-Cis reached statistical significance for the primary objective on the basis of a pre-specified interim analysis which was considered the final formal statistical analysis for OS.2
TOPAZ-1 is ongoing, allowing for further exploratory follow-up OS analysis.
Twice as many patients receiving the IMFINZI TOPAZ-1 regimen were alive at 2 years vs. placebo + Gem-Cis.1
Exploratory analysis demonstrated that OS favoured the IMFINZI TOPAZ-1 regimen vs. placebo + Gem-Cis in some predefined subgroups.†1
reduction in the risk of death with IMFINZI + Gem-Cis (n=341) vs. placebo + Gem-Cis (n=344, HR, 0.76 [95% CI 0.64–0.91]); ARR at 2 years=12.1%.†2
OS was not formally tested for statistical significance at this time. No p-value reported.
*OS was estimated using Kaplan-Meier curves and presented by treatment arm. At the interim analysis (data cut-off: August, 2021) OS was tested for superiority using a log-rank test stratified by disease status and primary tumour location; the OS p-value of 0.021 met the boundary for declaring statistical significance.1 At the updated analysis (data cut-off: February, 2022), OS was not formally tested for significance due to significance already being met at the earlier timepoint.2
†Not powered for statistical significance.
With 6.5 months of additional follow-up, the OS benefit with the addition of durvalumab to Gem-Cis numerically improved versus the interim analysis: HR, 0.76 (95% CI 0.64–0.91) from HR, 0.80 (95% CI 0.66–0.97) [p=0.021].1,2
The four-year OS exploratory analysis was conducted post hoc and was not powered for statistical significance.
(Data cut-off: 28 February 2025)
*OS was estimated using Kaplan-Meier curves and presented by treatment arm. At the interim analysis (data cut-off: August, 2021), median follow-up time was 16.8 months in the IMFINZI group vs. 15.9 months in the placebo group. OS was tested for superiority using a log-rank test stratified by disease status and primary tumour location; the OS p-value of 0.021 met the boundary for declaring statistical significance.1 At the updated analysis (data cut-off: 28 February, 2025), median (range) follow-up in censored patients was 56.9 months (1.7–67.2) in the IMFINZI group vs. 50.7 months (0.9–62.6) in the placebo group.
7.2 months
5.7 months
(Data cut-off: August, 2021)
HR, 0.75 (95% CI 0.63–0.89; p=0.001)†
Twice as many patients receiving IMFINZI + Gem-Cis were progression-free at one year vs. placebo + Gem-Cis.4
PFS curves demonstrated a statistically significant improvement for the IMFINZI regimen (7.2 [6.7–7.4] months) compared with placebo + Gem-Cis (5.7 [5.6–6.7] months).4
Exploratory analysis demonstrated that PFS favoured IMFINZI + Gem-Cis vs. placebo + Gem-Cis in some predefined subgroups.‡4
*PFS in the IMFINZI and placebo groups was investigator assessed according to RECIST v1.1 and defined as the time from date of randomisation until the date of RECIST v1.1-defined imaging disease progression or death.1,2,4
†The analysis for HR was performed using a stratified Cox proportional hazards model, and 2-sided P value is based on stratified log-rank test. Both are adjusted for disease status and primary tumour location. At the pre-planned interim analysis (data cut-off: August, 2021) the PFS p-value was 0.001, which met the boundary for declaring statistical significance.¹ PFS was not evaluated at the updated analysis (data cut-off: February, 2022).1,2,4
‡Not powered for statistical significance.1,2,4
1L, first line; BTC, biliary tract cancer; CI, confidence interval; eCCA, extrahepatic cholangiocarcinoma; ECOG, Eastern Cooperative Oncology Group; GBC, gallbladder cancer; Gem-Cis, gemcitabine-cisplatin; HR, hazard ratio; iCCA, intrahepatic cholangiocarcinoma; IO, immune-oncology; OS, overall survival; PS, performance status; Q3W, once every 3 weeks; Q4W, once every 4 weeks; R, randomisation; RECIST, response evaluation criteria in solid tumours; RWE, real-world evidence.
IMFINZI did not add additional toxicity to that observed with Gem-Cis, and the safety profiles of the two treatment groups were generally similar1
| Adverse event, n (%) | IMFINZI + Gem-Cis (n=338) | Placebo + Gem-Cis (n=342) |
| Any AE | 336 (99.4) | 338 (98.8) |
| Any TRAE | 314 (92.9) | 308 (90.1) |
| Any Grade 3/4 AE | 256 (75.7) | 266 (77.8) |
| Any Grade 3/4 TRAE | 212 (62.7) | 222 (64.9) |
| Any serious AE | 160 (47.3) | 149 (43.6) |
| Any serious TRAE | 53 (15.7) | 59 (17.3) |
| Any AE leading to discontinuation | 44 (13.0) | 52 (15.2) |
| Any TRAE leading to discontinuation | 30 (8.9) | 39 (11.4) |
| Any AE leading to death | 12 (3.6) | 14 (4.1) |
| Any TRAE leading to death | 2 (0.6) | 1 (0.3) |
| Any immune-mediated AE* | 43 (12.7) | 16 (4.7) |
AE incidence is greater in the IMFINZI group
AE incidence is greater in the placebo group
Data cut-off: August 11, 2021.
The median (range) duration of study treatment was 7.3 months (0.1–24.5) for durvalumab and 5.8 months (0.2–21.5) for placebo.
*Please see the IMFINZI Summary of Product Characteristics for further information on special warnings and precautions, including immune-mediated adverse events and their management.
The most common Grade 3–4 AEs were anaemia, neutropenia and decreased neutrophil count1
| Adverse events occurring in ≥10% of patients in either treatment arm | IMFINZI + Gem-Cis (n=338) | Placebo + Gem-Cis (n=342) | ||
|---|---|---|---|---|
| All grades (%) | Grade 3–4 (%) | All grades (%) | Grade 3–4 (%) | |
| Anaemia | 48.2 | 23.7 | 44.7 | 22.5 |
| Nausea | 40.2 | 1.5 | 34.2 | 1.8 |
| Constipation | 32.0 | 0.6 | 28.9 | 0.3 |
| Neutropenia | 31.7 | 20.1 | 29.8 | 21.1 |
| Neutrophil count decreased | 26.9 | 21.0 | 31.0 | 25.7 |
| Fatigue | 26.9 | 3.3 | 26.3 | 3.5 |
| Decreased appetite | 25.7 | 2.1 | 23.1 | 0.9 |
| Platelet count decreased | 20.7 | 9.8 | 23.1 | 8.5 |
| Pyrexia | 20.1 | 1.5 | 16.4 | 0.6 |
| Vomiting | 18.3 | 1.5 | 18.1 | 2.0 |
| Diarrhoea | 16.9 | 1.2 | 14.9 | 1.8 |
| Asthenia | 14.2 | 3.0 | 14.0 | 2.3 |
| Abdominal pain | 13.9 | 0.6 | 17.0 | 2.6 |
| Thrombocytopenia | 12.7 | 4.7 | 13.2 | 5.3 |
| Pruritus | 11.2 | - | 8.2 | - |
| Rash | 11.2 | 0.9 | 7.9 | 0 |
| White blood cell count decreased | 10.9 | 4.4 | 13.5 | 5.8 |
| Abdominal pain upper | 10.4 | 0 | 8.8 | 0.3 |
| Insomnia | 9.5 | - | 10.5 | - |
| ALT increased | 8.6 | 1.2 | 10.2 | 0.6 |
AE incidence is greater in the IMFINZI group
AE incidence is greater in the placebo group
Data cut-off: August 11, 2021.
Median duration of study treatment was 7.3 months (range: 0.1–24.5) for IMFINZI and 5.8 months (range: 0.2–21.5) for placebo.
13% of those in the IMFINZI arm experienced any grade imAE vs. 5% in the placebo arm1
| Adverse event, n (%) | IMFINZI + Gem-Cis (n=338) | Placebo + Gem-Cis (n=342) | ||
|---|---|---|---|---|
| Any grade | Grade ≥ 3 | Any grade | Grade ≥ 3 | |
| Any immune-mediated adverse event* | 43 (12.7) | 8 (2.4) | 16 (4.7) | 5 (1.5) |
| Hypothyroid events | 20 (5.9) | 0 (0) | 5 (1.5) | 0 (0) |
| Dermatitis/rash | 12 (3.6) | 3 (0.9) | 1 (0.3) | 0 (0) |
| Pneumonitis | 3 (0.9) | 1 (0.3) | 2 (0.6) | 1 (0.3) |
| Hepatic events | 4 (1.2) | 2 (0.6) | 2 (0.6) | 1 (0.3) |
| Adrenal insufficiency | 4 (1.2) | 0 (0) | 1 (0.3) | 0 (0) |
| Diarrhoea/colitis | 2 (0.6) | 1 (0.3) | 1 (0.3) | 1 (0.3) |
| Hyperthyroid events | 2 (0.6) | 0 (0) | 0 (0) | 0 (0) |
| Type 1 diabetes mellitus | 1 (0.3) | 1 (0.3) | 0 (0) | 0 (0) |
| Pancreatic events | 1 (0.3) | 0 (0) | 2 (0.6) | 1 (0.3) |
| Hypophysitis | 1 (0.3) | 0 (0) | 0 (0) | 0 (0) |
| Thyroiditis | 1 (0.3) | 0 (0) | 0 (0) | 0 (0) |
| Renal events | 0 (0) | 0 (0) | 2 (0.6) | 0 (0) |
| Myositis | 0 (0) | 0 (0) | 1 (0.3) | 1 (0.3) |
| Other rare/miscellaneous† | 1 (0.3) | 1 (0.3) | 1 (0.3) | 1 (0.3) |
imAE incidence is greater in the IMFINZI group
imAE incidence is greater in the placebo group
Please see the IMFINZI Summary of Product Characteristics for further information on special warnings & precautions, immune-mediate adverse events and their management.
Data cut-off: August 11, 2021.
Median duration of study treatment was 7.3 months (range: 0.1–24.5) for IMFINZI and 5.8 months (range: 0.2–21.5) for placebo.
*An immune-mediated adverse event is defined as an event associated with drug exposure and is accompanied by an immune-mediated mechanism of action, with no clear alternate aetiology.
†The events in the “other rare/miscellaneous” category were immune-mediated arthritis in the IMFINZI group and arthritis in the placebo group.
Discontinuations due to adverse events of any cause1
(13.0%) with IMFINZI + Gem-Cis
(15.2%) with Gem-Cis
Data cut-off: 11 August, 2021
The rate of SAEs possibly related to treatment was similar between treatment arms and consistent with the safety profile observed at previous analyses1–3
| Exploratory analysis | |||||||||
| DCO: February 28, 2025*2,3 | DCO: October 23, 2023*2,3 | DCO: February 25, 2022*3 | DCO: August 11, 20211,3 | ||||||
| Adverse event, n (%) | IMFINZI + Gem-Cis (n=338) | Placebo + Gem-Cis (n=342) | IMFINZI + Gem-Cis (n=338) | Placebo + Gem-Cis (n=342) | IMFINZI + Gem-Cis (n=338) | Placebo + Gem-Cis (n=342) | IMFINZI + Gem-Cis (n=338) | Placebo + Gem-Cis (n=342) | |
| Any SAE | 168 (49.7) | 152 (44.4) | 165 (48.8) | 152 (44.4) | 161 (47.6) | 151 (44.2) | 160 (47.3) | 149 (43.6) | |
| Treatment-related SAEs† | 52 (15.4) | 59 (17.3) | 52 (15.4) | 59 (17.3) | 52 (15.4) | 59 (17.3) | 53 (15.7) | 59 (17.3) | |
SAE/TRSAE incidence is greater in the IMFINZI group
SAE/TRSAE incidence is greater in the placebo group
At the four-year follow-up, the average duration of exposure to IMFINZI or placebo was 7.3 months (0.1–65.2) with IMFINZI + Gem-Cis and
5.8 months (0.2–28.4) with placebo + Gem-Cis2
Safety data percentages are calculated from the safety population (n=338 for IMFINZI + Gem-Cis and n=342 for placebo + Gem-Cis); SAE data was the only type of AE data reported after the February 25, 2022 data cut-off. Two new AEs with the outcome of death were reported in IMFINZI + Gem-Cis since the primary analysis (data cut-off: August 11, 2021), both unrelated to study treatment.
*The February 28, 2025; October 23, 2023; and February 25, 2022 data cut-offs were exploratory analyses with no formal statistical testing.
†As assessed by the investigator.
AE, adverse event; ALT, alanine aminotransferase; DCO, data cut-off; Gem-Cis, gemcitabine-cisplatin; imAE, immune-mediated adverse event; SAE, serious adverse event; TR(S)AE, treatment-related (serious) adverse event.
GB-73556 | March 2026
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GB-74216| DOP : February 2026
