2800 - IMvigor130: efficacy and safety from a Phase 3 study of atezolizumab (atezo) as monotherapy or combined with platinum-based chemotherapy (PBC) vs placebo + PBC in previously untreated locally advanced or metastatic urothelial carcinoma (mUC)

Background

First-line (1L) mUC treatment (tx) includes cisplatin (cis)- or carboplatin (carbo)-based chemotherapy or checkpoint inhibitors, depending on patient (pt) eligibility and PD-L1 status. IMvigor130 is a phase 3, global, multicentre, randomised, partially blinded study evaluating atezo (anti–PD-L1) alone or with PBC vs placebo + PBC in untreated mUC.

Methods

IMvigor130 enrolled 1213 PBC-eligible pts with mUC. Pts were randomised 1:1:1 to Arm A (atezo + PBC [gemcitabine (gem) + either cis or carbo]), Arm B (atezo) or Arm C (placebo + PBC). Gem 1000 mg/m² IV was given on Day (D) 1 and D8, carbo AUC 4.5 IV or cis 70 mg/m² IV on D1 and atezo/placebo or atezo 1200 mg IV on D1 of each 3-wk tx cycle. Tumours were assessed at baseline and every 9 wk until (INV)-assessed PD per RECIST 1.1 or other events. Coprimary efficacy endpoints are INV-assessed PFS and OS (Arm A vs C) and OS (Arm B vs C, hierarchical approach) per RECIST 1.1. Final PFS (Arm A vs C) and interim OS are shown here.

Results

With a median follow-up of 11.8 mo, median PFS was 8.2 mo in Arm A vs 6.3 mo in Arm C (HR, 0.82 [95% CI: 0.70, 0.96]; P = 0.007). The comparison of OS did not cross the prespecified interim efficacy boundary, with a median of 16.0 mo in Arm A and 13.4 mo in Arm C (HR, 0.83 [95% CI: 0.69, 1.00]; P = 0.027; Table). For Arm B vs C, the median OS was 15.7 and 13.1 mo, respectively (HR, 1.02 [95% CI: 0.83, 1.24]), for ITT pts and not estimable and 17.8 mo, respectively (HR, 0.68 [95% CI: 0.43, 1.08]), for PD-L1 IC2/3 pts. ORRs were 47%, 23% and 44% and CR rates were 13%, 6% and 7% for Arms A, B and C, respectively. AEs that led to tx withdrawal occurred in 34%, 6% and 34% of pts in Arms A, B and C, respectively.Table:

LBA14_PR

Stratification factors were PD-L1 status on tumour-infiltrating immune cells (IC; IC0 vs IC1 vs IC2/3), Bajorin risk factors/liver metastases (0 vs 1 vs 2 or pts with liver metastases) and investigator (INV)-specified PBC (gem + carbo vs gem + cis). Data cutoff: 31 May 2019.

PFS and OS for Arm A vs C were formally tested with type I error control for multiple comparisons with a prespecified interim efficacy boundary P value of 0.007; Arm B vs C in ITT and PD-L1 IC2/3 pts were not formally tested.

Conclusions

Adding atezo to PBC for 1L mUC tx prolonged PFS vs PBC alone in pts with untreated mUC. The combination safety profile was consistent with that observed for the individual agents.

Clinical trial identification

NCT02807636.

Editorial acknowledgement

Medical writing assistance was provided by Paige Davies, PhD, of Health Interactions, and funded by F. Hoffmann-La Roche, Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.

Funding

F. Hoffmann-La Roche, Ltd.

Disclosure

E. Grande: Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (self): Ipsen; Speaker Bureau / Expert testimony: BMS; Speaker Bureau / Expert testimony: Eisai; Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Speaker Bureau / Expert testimony, Research grant / Funding (institution): MSD; Speaker Bureau / Expert testimony: Sanofi-Genzyme; Speaker Bureau / Expert testimony: Adacap; Speaker Bureau / Expert testimony: Novartis; Speaker Bureau / Expert testimony: EUSA Pharma; Speaker Bureau / Expert testimony: Pierre Fabre; Speaker Bureau / Expert testimony, Research grant / Funding (self): Lexicon; Speaker Bureau / Expert testimony: Celgene; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): MTEM/Threshold; Advisory / Consultancy: Enets; Officer / Board of Directors: Getne; Officer / Board of Directors: Gethi. M. Galsky: Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Dendreon; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: BioMotiv; Advisory / Consultancy: Glaxo Smith Kline; Advisory / Consultancy: Lilly; Advisory / Consultancy: Astellas; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: EMD-Serono; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Incyte; Advisory / Consultancy: Aileron; Advisory / Consultancy: Dracen; Advisory / Consultancy: Inovio; Advisory / Consultancy: Dragonfly. J.A. Arranz Arija: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pierre Fabre Oncology; Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self): Roche; Honoraria (self): Cilag; Travel / Accommodation / Expenses: Essa; Travel / Accommodation / Expenses: Ferring. M. De Santis: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen, Astellas, AstraZeneca, Bayer, Bioclin; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: BMS, EISAI, Roche; Honoraria (self), Travel / Accommodation / Expenses: Clovis, Incyte; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: ESSA; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ferring; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: OncoGenex; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre Oncology; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sandoz; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: SeaGen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Shionogi, Synthon, Takeda; Non-remunerated activity/ies: EAU Prostrate Cancer Guidelines; Non-remunerated activity/ies: ESMO Bladder Cancer Practice Guidelines; Non-remunerated activity/ies: S3 Blasenkarzinom Leitlinien. I.D. Davis: Honoraria (institution), Advisory / Consultancy: Amrad; Honoraria (institution), Advisory / Consultancy: Sanofi (and Sanofi-aventis); Honoraria (institution), Advisory / Consultancy: NovoNordisk; Honoraria (institution), Advisory / Consultancy: Bayer; Honoraria (institution), Advisory / Consultancy: Pharmion ; Honoraria (institution), Advisory / Consultancy: Wyeth; Honoraria (institution), Advisory / Consultancy: Schering-Plough; Honoraria (institution), Advisory / Consultancy: Novartis; Honoraria (institution), Advisory / Consultancy: GSK; Honoraria (institution), Advisory / Consultancy: Medivation; Honoraria (institution), Advisory / Consultancy: Janssen; Honoraria (institution), Advisory / Consultancy: Dendreon; Honoraria (institution), Advisory / Consultancy: Ipsen; Honoraria (institution), Advisory / Consultancy: Astellas; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: Eisai; Honoraria (institution), Advisory / Consultancy: Pfizer; Honoraria (institution), Advisory / Consultancy: BMS, AstraZeneca; Research grant / Funding (institution): NHMRC Practitioner Fellowship; Officer / Board of Directors: Anzup. U.F.F. De Giorgi: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy: Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. M. Mencinger: Advisory / Consultancy: Sanofi; Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Speaker Bureau / Expert testimony: roche; Honoraria (self), Speaker Bureau / Expert testimony: Janssen; Honoraria (self), Speaker Bureau / Expert testimony: Astellas. E. Kikuchi: Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution): Nippon; Research grant / Funding (institution): Kayaku; Honoraria (self), Research grant / Funding (institution): Astellas; Honoraria (self), Research grant / Funding (institution): ONO; Honoraria (self), Research grant / Funding (institution): Chugai; Honoraria (self), Research grant / Funding (institution): Takeda; Honoraria (self), Research grant / Funding (institution): Taiho; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Kissei; Honoraria (self): ASKA; Honoraria (self): Shinyaku; Honoraria (self): Pfizer. X. Garcia del Muro: Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy: Lilly; Advisory / Consultancy: Pharmamar; Advisory / Consultancy: Eusapharma; Honoraria (self), As a speaker or moderator in Scientific Meeting: Astellas. M. Gumus: Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen. M. Özgüroğlu: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Sanofi; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Astellas; Honoraria (self), Honoraria (institution): Novartis; Honoraria (self), Honoraria (institution): Roche; Travel / Accommodation / Expenses: BMS. A. Rezazadeh Kalebasty: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genentech, Inc./Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Exelixis; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Eisai; Research grant / Funding (institution): Macrogenics; Honoraria (self), Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Research grant / Funding (institution): beyond spring; Research grant / Funding (institution): Bioclin; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Bavarian Nordic; Research grant / Funding (institution): Seattle Genetics; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Speaker Bureau / Expert testimony: Amgen; Shareholder / Stockholder / Stock options: ECOM; Honoraria (self), Speaker Bureau / Expert testimony: Sanofi; Travel / Accommodation / Expenses: Prometheus Labs. B.Y. Alekseev: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ferring. F.A.B. Schutz: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Spouse / Financial dependant: Ipsen. A. Mecke: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: F. Hoffmann-La Roche. S. Mariathasan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Roche/GNE. A. Thastrom: Shareholder / Stockholder / Stock options, Full / Part-time employment: Genentech, Inc.. A. Bamias: Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self), Research grant / Funding (institution): AstraZeneca. All other authors have declared no conflicts of interest.