Browsing Over 191 Presentations
Monitoring anti tumour T cell immunity
- Pia Kvistborg
- Pia Kvistborg
Deciphering the immunopeptidome of human cancers
- Michal Bassani-Sternberg
- Michal Bassani-Sternberg
Clonal neoantigens in cancer immunotherapy
- Sergio Quezada
- Sergio Quezada
Learning from tumour microenvironment to inform therapy
- George Coukos
- George Coukos
Kick the immune system with immunocytokines
- Dario Neri
- Dario Neri
Release the brake with checkpoint inhibitors
- Inge Verbrugge
- Inge Verbrugge
Optimal trial design for radiotherapy and immune treatment
- Eric Deutsch
- Eric Deutsch
The immunogenic effects of VEGF targeted therapy: Fact or fiction?
- Thomas Powles
- Thomas Powles
Invited Discussant LBA1_PR
- Solange Peters
- Naiyer Rizvi
- Solange Peters
- Naiyer Rizvi
Primary PFS and safety analyses of a randomized Phase III study of carboplatin + paclitaxel +/− bevacizumab, with or without atezolizumab in 1L non-squamous metastatic NSCLC (IMpower150)
- Martin Reck
- Martin Reck
- Mark A. Socinski
- Federico Cappuzzo
- Francisco Orlandi
- Daniil Stroyakovskii
- Naoyuki Nogami
- Delvys Rodríguez-Abreu
- Denis Moro-Sibilot
- Christian A. Thomas
- Fabrice Barlesi
- Gene Finley
- Claudia Kelsch
- Anthony Lee
- Shelley Coleman
- Yijing Shen
- Marcin Kowanetz
- Ariel Lopez-Chavez
- Alan Sandler
- Robert Jotte
Abstract
Background
Atezolizumab (atezo; anti–PD-L1) inhibits PD-L1 binding to PD-1 and B7.1, restoring anti-cancer immunity. Bev may further enhance atezo efficacy by inhibiting VEGF immunosuppression and promoting T-cell tumour infiltration. IMpower150 evaluates the addition of atezo to carboplatin (C) + paclitaxel (P) ± bevacizumab (bev) in chemo-naive patients (pts) with non-squamous (NSQ) mNSCLC.
Methods
1202 pts received atezo 1200 mg + C AUC 6 + P 200 mg/m2 (Arm A) or atezo + bev 15 mg/kg + C + P (Arm B) vs bev + C + P (Arm C) IV q3w for 4 or 6 cycles per investigator (INV) discretion, then maintenance atezo, atezo + bev or bev, respectively. Co-primary endpoints assessed at this data cutoff (15 Sep 2017; minimum follow up, 9.5 mo) were INV-assessed PFS in the ITT-WT (EGFR or ALK negative) population and in WT pts with expression of a tumour T-effector gene signature (Teff-WT; centrally assessed), and OS in the ITT-WT population, for the Arm B vs Arm C comparison. Due to pre-specified statistical testing hierarchy, Arm A vs Arm C has not been formally tested yet.
Results
356 pts in Arm B and 336 pts in Arm C were enrolled in the ITT-WT. Median age was 63 y; 60% were previous smokers (both arms). 61% and 62% were male, and 39% and 43% had ECOG PS 0 in Arms B and C, respectively. The HRs for INV-assessed PFS in Arm B vs C were 0.62 (95% CI: 0.52, 0.74; P < 0.0001) in the ITT-WT and 0.51 (0.38, 0.68; P < 0.0001) in the Teff-WT populations. Median PFS in Arm B vs C was 8.3 mo vs 6.8 mo and 11.3 mo vs 6.8 mo in the ITT-WT and Teff-WT populations, respectively. PFS benefit was seen regardless of PD-L1 IHC status, including PD-L1–negative pts (TC0/IC0; HR, 0.77 [95% CI: 0.61, 0.99]). Landmark PFS and ORR are shown (Table). Arm B had a comparable safety profile to Arm C; treatment-related serious AEs were 25% vs 19%, respectively.
Conclusions
IMpower150 is the first Ph 3 study to show a statistically significant and clinically meaningful PFS benefit with atezo + bev + chemo vs bev + chemo in pts with 1L NSQ mNSCLC.
Table. IMpower150 Primary PFS Analysis, landmark PFS and ORR | ||
Arm C | Arm B | |
ITT-WT populationa | n = 336 | n = 356 |
Median PFS (95% CI), mo | 6.8 (6.0, 7.1) | 8.3 (7.7, 9.8) |
HR (95% CI; P value) | 0.62 (0.52, 0.74; P < 0.0001) | |
ITT-WT landmark PFS (95% CI), % | ||
6-month | 56% (51, 62) | 67% (62, 72) |
12-month | 18% (13, 23) | 37% (31, 42) |
ORRb,c (95% CI), % | 48% (43, 54) | 64% (58, 68) |
Teff-WT populationa | n = 129 | n = 155 |
Median PFS (95% CI), mo | 6.8 (5.9, 7.4) | 11.3 (9.1, 13.0) |
HR (95% CI; P value) | 0.51 (0.38, 0.68; P < 0.0001) | |
Teff-WT landmark PFS (95% CI), % | ||
6-month | 57% (48, 66) | 72% (65, 79) |
12-month | 18% (10, 25) | 46% (38, 54) |
ORRb,d (95% CI), % | 54% (44, 62) | 69% (61, 76) |
DOR, duration of response; HR, hazard ratio; ORR, objective response rate; PFS, progression-free survival; Teff, T-effector; WT, wild-type. |
Clinical trial identification
NCT02366143
Response, progress and survival as endpoints for immuno-oncology therapy trials
- Naiyer Rizvi
- Naiyer Rizvi
How can we obtain accurate efficacy data from early phase trials
- Thomas Powles
- Thomas Powles