METΔ14ex is the driver alteration for approximately 3% of non-small cell lung cancers (NSCLC) and associated with a higher PD-L1 expression, but unclear benefit from immunotherapy (IO). Seventy-eight consecutive patients with metastatic NSCLC harboring METΔex14 who received first-line IO as monotherapy or chemoimmunotherapy (CHT+IO) in 10 German academic lung cancer centers were analyzed. The median age was 72 years (range 49-86), 34 patients (44%) were female, 47 (60%) were active or former smokers, and 23 (29%) presented with brain metastases. The Eastern Cooperative Group (ECOG) performance status was 0, 1, 2 and 3 in 27 (35%), 28 (36%), 18 (23%) and 4 (5%) cases, respectively. The most common histology was adenocarcinoma (n=61, 78%). IO was given to 43 (55%) patients as monotherapy, and to 35 (45%) combined with CHT. For patients with PD-L1 tumor proportion score (TPS) ≥50% (n=52, 67%), 1-49% (n=14, 18%) and <1% (n=12, 15%), disease control rates (DCR) were 56%, 57% and 100% (p=0.015), respectively. Other efficacy parameters including overall response rate (ORR), median progression-free survival (mPFS) and median overall survival (mOS) by PD-L1 tumor proportion score (TPS) and type of treatment are summarized in the table. Primary progressive disease/early death (before radiologic reassessment) under IO monotherapy, but not under CHT+IO, was significantly associated with never-smoker status (p=0.041). No significant correlations were found between smoking status and PD-L1 TPS (p=0.595). Table: 54PTPS≥50% / IO n=43TPS≥50% / CHT+IO n=9TPS 1-49% / CHT+IO n=14TPS 0% / CHT+IO n=12p-valueORR (%)355643500.599DCR (%)5467571000.030mPFS (mo)346150.520mOS (mo)14515160.690 Open table in a new tab Our exploratory analysis suggests an association between higher PD-L1 TPS and worse clinical outcomes under IO in patients with NSCLC harboring METΔ14ex. Although these results should be interpreted with caution, they contrast the favorable effect of PD-L1 expression for IO efficacy in other NSCLC and underline the need for alternative biomarkers for IO in this patient population.

Abstract Background TP53 mutations are associated with adverse outcome of AML treated with cytarabine-based regimens. Interestingly, DNA-hypomethylating agents (HMAs) induce a higher response rate in TP53-mutated (MUT) compared to TP53 wildtype (WT) AML (Welch et al., N. Engl. J. Med. 2016, Döhner et al., Leukemia 2018). We conducted a randomized phase II trial (NCT00867672, 2x2 factorial design) asking whether the in vitro cooperativity of DAC with VPA or ATRA translates into clinical benefit. While VPA added to DAC affected neither objective response rate (ORR) nor overall survival (OS), ATRA significantly improved ORR and OS, without added toxicity (Lübbert et al., J. Clin. Oncol. 2020). Preclinical data suggest that HMAs and ATRA have cooperative effects also in TP53 MUT AML. We therefore performed a post-hoc analysis to determine the predictive impact of TP53 status. Patients and Methods Key inclusion criteria: newly diagnosed AML pts >60 yr (non-M3) unfit for induction, ECOG performance status (PS) 0-2. Treatment: DAC 20 mg/m 2 day 1-5 (arms A/B/C/D), VPA p.o. from day 6 (arms B/D), ATRA p.o. day 6-28 (arms C/D) of each 28-day course. For TP53 mutation analyses, the Illumina TruSight Myeloid Sequencing Panel was used for library preparation and an Illumina MiSeq device for sequencing. Key endpoints: ORR (CR/CRi/PR, ELN 2010 criteria) and OS. Original sample size calculation of a total of 200 patients (pts) was based on the primary endpoint ORR (Lübbert et al., Haematologica 2012). ORR was analyzed with logistic regression, OS with Cox regression. Odds ratios (OR) for the effect on ORR and hazard ratios (HR) for the effect on death with 95% confidence intervals (CI) are presented in the genetic subgroups TP53 MUT and TP53 WT including tests for interactions (TFI) between treatment and TP53. These are post-hoc exploratory analyses, hence p-values have to be interpreted in a descriptive sense. Results Between 12/2011 and 2/2015, 200 pts were randomized and treated. Information on TP53 status was available for 168 of 200 pts (84%); 155 of them (92%) had died at last follow-up (June 2021). 61% of pts were aged >75 years (range 61-92), ECOG PS 0/1/2: 19/62/19% (a single pt had a PS of 3); 53% had an HCT-CI >3, 19% WBC >30.000/µl, 30% adverse genetics (ELN 2010), 51% an antecedent hematologic disorder. TP53 aberrations were detected in 42 pts (25%), with 1 (n=27) or 2 mutations (n=12, median variant allele frequency 44%, range, 1.3-99%) in 39 pts, and TP53 deletions in 3 additional pts. The 42 pts with TP53 MUT showed a higher ORR (23.8%) than the 126 pts with TP53 WT (ORR 15.1%), with an OR of 2.04 (95% CI 0.83-4.98), p=0.12. OS (irrespective of treatment) in the TP53 MUT v WT pts was not different (HR, adjusted for treatment: 1.14 [95% CI 0.78-1.66], p=0.51; Fig. A). In both genetic groups, the addition of ATRA had a favorable effect on ORR (ATRA v no ATRA in TP53 MUT: 31.3% v 19.2%, OR 1.91 [95% CI 0.45-8.03]; ATRA v no ATRA in TP53 WT: 18.8% v 10.5%, OR 1.98 [95% CI 0.70-5.61]), TFI p=0.97 (Fig. B). A positive effect of ATRA on OS in both genetic groups was reflected by a median OS of 6.0 v 4.5 months (ATRA v no ATRA in TP53 MUT: HR 0.75 [95% CI 0.38-1.48]), and a median OS of 8.9 v 4.7 months (ATRA v no ATRA in TP53 WT: HR 0.58 [95% CI 0.39-0.86], all results adjusted for VPA, ECOG, HCT-CI, sLDH, Hb), TFI p=0.49 (Fig. C). VPA did not affect ORR in either of the 2 genetic groups (VPA v no VPA in TP53 MUT: 21.7% v 26.3%, OR 0.76 [95% CI 0.18-3.21]; VPA v no VPA in TP53 WT: 16.7% v 13.3%, OR 1.34 [95% CI 0.5-3.61]), TFI p=0.53. The impact of VPA on OS differed between TP53 MUT pts (VPA v no VPA: median OS of 4.2 v 5.3 months, HR 1.31 [95% CI 0.69-2.48], and TP53 WT pts (VPA v no VPA: median OS of 8.4 v 4.8 months, HR 0.67 [95% CI 0.46-0.99], all results adjusted for ATRA, ECOG, HCT-CI, sLDH, Hb; TFI p=0.08, Fig. C). Conclusions Our results confirm the reported higher response rate to DAC in pts with TP53 MUT compared to TP53 WT; the addition of ATRA led to a higher ORR. Improved OS with ATRA was observed particularly in TP53 WT pts. In contrast, VPA did not affect the ORR in either genetic group; TP53 WT pts may benefit from VPA regarding OS. Our exploratory post-hoc results need confirmation in other trials, e.g. in the DECIDER-2 study (adding ATRA or placebo to the recently approved dual treatment of a HMA combined with venetoclax). Cooperative effects of HMAs and retinoids deserve a deeper mechanistic understanding, which may have implications not only for AML but also for other malignancies with impaired TP53. Figure 1 Figure 1. Disclosures Becker: BMS: Honoraria; Pierre Fabre Pharma: Honoraria; Servier: Honoraria; MSD: Honoraria; Novartis: Honoraria. Crysandt: Incyte: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees. Thol: Abbvie: Honoraria; Pfizer: Honoraria; Astellas: Honoraria; Novartis: Honoraria; BMS/Celgene: Honoraria, Research Funding; Jazz: Honoraria. Heuser: Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Tolremo: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Research Funding; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; BergenBio: Research Funding; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer Pharma AG: Research Funding; Astellas: Research Funding. Goetze: Abbvie: Other: Advisory Board; BMS/Celgene: Other: Advisory Board, Research Funding. Schlenk: Agios: Honoraria; Astellas: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria; Daiichi Sankyo: Honoraria, Research Funding; Abbvie: Honoraria; Hexal: Honoraria; Neovio Biotech: Honoraria; Novartis: Honoraria; Pfizer: Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria, Research Funding; AstraZeneca: Research Funding; Boehringer Ingelheim: Research Funding. Salih: Synimmune GmbH: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; Celgene: Honoraria; BMS: Honoraria. Schittenhelm: Takeda: Other: advisory board; Astellas: Other: advisory board; BMS: Other: advisory board; University of Tuebingen: Patents & Royalties: patent for ASPP2k. Müller-Tidow: Pfizer: Research Funding; Janssen: Consultancy, Research Funding; Bioline: Research Funding. Germing: Novartis: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria, Other: advisory activity, Research Funding. Giagounidis: Novartis: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Wäsch: Amgen: Consultancy, Honoraria; Pfizer: Consultancy; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Novartis: Consultancy; BMS/Celgene: Consultancy; Gilead: Consultancy. Döhner: Jazz Roche: Consultancy, Honoraria; Celgene/BMS: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Other: Advisory Board; Agios and Astex: Research Funding; Abbvie: Consultancy, Honoraria; Janssen: Honoraria, Other: Advisory Board; Astellas: Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Ganser: Novartis: Honoraria; Jazz Pharmaceuticals: Honoraria; Celgene: Honoraria. Döhner: Astellas: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Oxford Biomedicals: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Research Funding; Helsinn: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding; Berlin-Chemie: Consultancy, Honoraria; Astex: Consultancy, Honoraria; Agios: Consultancy, Honoraria, Research Funding; Ulm University Hospital: Current Employment; Jazz: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria; GEMoaB: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Pfizer: Research Funding. Hackanson: Roche: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Boehringer-Ingelheim: Consultancy, Honoraria; MSD: Consultancy, Honoraria. Lübbert: Cheplapharm: Other: study drug (ATRA); TEVA: Other: study drug (valproic acid); Janssen: Consultancy, Other: study drug (decitabine), Research Funding; Syros: Consultancy, Honoraria; Aristopharm: Other: study drug ; Imago BioSciences: Consultancy, Other: study support with study drug; AbbVie: Consultancy, Honoraria; Astex: Consultancy, Honoraria. OffLabel Disclosure: ATRA, in non-M3 AML valproic acid, in non-M3 AML

BACKGROUND:Resection of liver metastases from colorectal cancer (CRC) in the oligometastatic stage improves survival and is a potentially curative treatment. Thus, predictive scores that reliably identify those patients who especially benefit from surgery are essential.PATIENTS AND METHODS:In this multicenter analysis, 512 patients had undergone surgery for liver metastases from CRC. We investigated distinct cancer-specific risk factors that are routinely available in clinical practice and developed a predictive preoperative score using a training cohort (TC), which was thereafter tested in a validation cohort (VC).RESULTS:Inflammatory response to the tumor, a right-sided primary tumor, multiple liver metastases, and node-positive primary tumor were significant adverse variables for overall survival (OS). Patients were stratified in five groups according to the cumulative score given by the presence of these risk factors. Median OS for patients without risk factors was 133.8 months [95% confidence interval (CI) 81.2-not reached (nr)] in the TC and was not reached in the VC. OS decreased significantly for each subsequent group with increasing number of risk factors. Median OS was significantly shorter (P < 0.0001) for patients presenting all four risk factors: 14.3 months (95% CI 10.5 months-nr) in the TC and 16.6 months (95% CI 14.6 months-nr) in the VC.CONCLUSIONS:Including easily obtainable variables, this preoperative score identifies oligometastatic CRC patients with prolonged survival rates that may be cured, and harbors potential to be implemented in daily clinical practice.

Combining anti-VEGF/Ang2 and anti-PD-1 therapy promotes an immunopermissive state, supportive of T-cell-mediated tumour cell destruction. This phase Ib study is assessing BI 836880 plus ezabenlimab in patients (pts) with advanced solid tumours. In Part 1 (dose escalation in pts with advanced NSCLC), the recommended phase 2 dose (RP2D) was determined as BI 836880 720 mg + ezabenlimab 240 mg IV q3w. Here, we report updated results, including data from Part 2 (expansion cohorts).

Objective. Resection remains the most important form of treatment for patients with intracranial malignancies. The advantages of surgical resection must be balanced with the risk of surgery. Intraoperative neuromonitoring (IOM) is utilized to improve safety and enlarge the resection extent. However, comparative data on the use if IOM is scarce.Methods. Retrospective analysis of patients following resection of motor eloquent lesions between June 2018 and June 2020 was performed. A comparative analysis of the extend of resection; neurological squeal were compared between resections with or without IOM.Results. 66 patients (31 female, 35 male, age median, SD 62+/− 11,2) were identified. IOM was performed in 34 (51%) cases. 46% were female with a median age of 62 (range 31–82). There were no differences in baseline patient“s characteristics between both groups. 14% and 3% had a temporary neurological deterioration in the IOM and non-IOM group (P = 0,198), respectively. 3% and 15% had a permanent neurological in the IOM and non-IOM group, respectively (P = 0.100). 65% and 35% of resections were total and subtotal in both the IOM and non-IOM group (P =  0.027), respectively.Conclusion. IOM is associated with lower rates of new postoperative neurological deterioration with the same rate resection quality following resection of motor eloquent lesions.

Preclinical studies have shown that combining anti-VEGF/Ang2 with anti-PD-1 therapy promotes an immunopermissive state supportive of T-cell-mediated tumour cell destruction. BI 836880 is a humanized bispecific nanobody® that targets VEGF and Ang2, and BI 754091 is an anti-PD-1 antibody. Dose-finding trials of BI 836880 and BI 754091 in advanced solid tumours determined the recommended phase II dose (RP2D) for monotherapy as 720 mg q3w and 240 mg q3w, respectively. Here, we report results from a phase Ib study assessing BI 836880 in combination with BI 754091. In part 1 (dose escalation), pts with locally advanced or metastatic (m) non-squamous NSCLC who progressed during/after completion of ≥2 cycles of platinum-based chemotherapy (CT) ± a checkpoint inhibitor (CPI) received BI 836880 plus fixed-dose BI 754091. RP2D was determined as BI 836880 720 mg plus BI 754091 240 mg q3w. In Part 2 (expansion phase), patients are recruited to one of 7 cohorts: mNSCLC after CPI monotherapy; mNSCLC after CT + CPI; mSCLC after CT ± CPI; immunotherapy-resistant m-melanoma; recurrent glioblastoma after 1st-line CT; HCC after prior sorafenib or lenvatinib; and previously untreated/unresectable HCC. At data cut-off (April 2020), 18 pts had received BI 836880 plus BI 754091 (14 in Part 1, 4 in Part 2); 11 males; median age 59 years, 13 had received prior CPI. Seven pts remain on treatment (including 1 treated for >12 months). 16 pts experienced an adverse event (AE; any-cause), most commonly (all%/G3%) hypertension (50/28), asthenia (33/6), vomiting, nausea and cough (each 33/0). No G4 AEs were reported; 2 G5 AEs occurred (1 general physical health deterioration and 1 tracheal haemorrhage). 6 pts had immune-related AEs (including G2 hypothyroidism; G2 pruritus, G2 vomiting, G1 papular rash). To date, 3 pts have achieved confirmed partial response (two NSCLC pts in Part 1, one 2nd-line HCC pt in Part 2), 10 pts had stable disease, 3 had progressive disease; data were not available for 2 pts. The combination of BI 836880 and BI 754091 had a manageable safety profile, and preliminary antitumor activity was observed. Expansion cohorts are ongoing.

Background Preclinical evidence shows that vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2) promote an immunosuppressive state in the tumour microenvironment, and that the combination of anti-VEGF/Ang2 with anti-PD-1 therapy promotes an immunopermissive state supportive of T-cell mediated tumour cell killing. BI 836880, a humanised bispecific nanobody that targets VEGF and Ang2, and BI 754091, an anti-PD-1 antibody, have shown safety and preliminary antitumour activity as monotherapies in phase I studies (RP2D, 720 mg iv q3w for BI 836880 and 240 mg iv q3w for BI 754091). The safety and efficacy of BI 836880 + BI 754091 are being assessed in this phase Ib trial in patients (pts) with advanced solid tumours. Trial design This open-label, dose-escalation/cohort-expansion trial is being conducted in two parts: Part 1, dose escalation of BI 836880 with BI 754091 in pts with advanced/metastatic, PD-L1 positive, nonsquamous NSCLC; Part 2, exploratory expansion cohorts (A–F) in 6 pt populations (A: metastatic [m] NSCLC after checkpoint inhibitor [CPI] monotherapy; B: mNSCLC after chemotherapy [CTX] + CPI; C: mSCLC after CTX with/without CPI; D: immunotherapy-resistant m-melanoma; E: recurrent glioblastoma after 1st line CTX; F: hepatocellular carcinoma after prior sorafenib or lenvatinib with/without subsequent CPI therapy). In Part 1, pts will receive BI 836880 (cohorts of 360, 500 and 720 mg iv q3w) + fixed-dose BI 754091 240 mg iv q3w, following a Bayesian logistic regression model with overdose control, with oversight from a safety monitoring committee. The primary endpoint in Part 1 is the MTD/RP2D, based on DLTs in Cycle 1. In Part 2, pts will receive BI 836880 at the RP2D + BI 754091 240 mg iv q3w. The primary endpoint in Part 2 is objective response; secondary endpoints are disease control, duration of response, PFS and tumour shrinkage. Safety, PK and exploratory biomarkers will be assessed. ∼220 pts will enroll globally: 20–25 pts in Part 1 and ∼200 in Part 2 (40 in Cohorts A/B; 30 in Cohorts C–F). As of May 2019, 6 pts have been treated in Part 1. Part 2 will begin once the RP2D is established in Part 1. Updates will be presented. Clinical trial identification NCT03468426. Editorial acknowledgement Fiona Scott, PhD, of GeoMed, an Ashfield company, part of UDG Healthcare plc; supported financially by Boehringer Ingelheim. Legal entity responsible for the study Boehringer Ingelheim. Funding Boehringer Ingelheim GmbH & Co, Ingelheim, Germany. Disclosure N. Girard: Advisory / Consultancy, Research grant / Funding (self), Corporate sponsored research, Advisory council or committee, Consulting fee, Grants or funds: BMS; Advisory / Consultancy, Research grant / Funding (self), Corporate sponsored research, Advisory council or committee, Consulting fee, Grants or funds: Boehringer; Advisory / Consultancy, Research grant / Funding (self), Corporate sponsored research, Advisory council or committee, Consulting fee: MSD; Advisory / Consultancy, Research grant / Funding (self), Corporate sponsored research, Advisory council or committee, Consulting fee, Grants or funds: Roche; Advisory / Consultancy, Research grant / Funding (self), Corporate sponsored research, Advisory council or committee, Consulting fee, Grants or funds: AstraZeneca. B. Hackanson: Honoraria (self), Advisory / Consultancy: Boehringer; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Roche. M. Wermke: Honoraria (self): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self): BMS; Honoraria (self): Roche; Honoraria (self): Glenmark; Honoraria (self): Kite; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Gemoab. F. Barlesi: Honoraria (self), Honoraria (institution): AstraZeneca; Honoraria (self), Honoraria (institution): Bristol-Myers Squibb; Honoraria (self), Honoraria (institution): Boehringer–Ingelheim; Honoraria (self), Honoraria (institution): Eli Lilly Oncology; Honoraria (self), Honoraria (institution): F. Hoffmann–La Roche Ltd; Honoraria (self), Honoraria (institution): Novartis; Honoraria (self), Honoraria (institution): Merck; Honoraria (self), Honoraria (institution): MSD; Honoraria (self), Honoraria (institution): Pierre Fabre; Honoraria (self), Honoraria (institution): Pfizer; Honoraria (self), Honoraria (institution): Takeda; Honoraria (institution): AbbVie; Honoraria (institution): ACEA; Honoraria (institution): Amgen; Honoraria (institution): Bayer; Honoraria (institution): Eisai; Honoraria (institution): Genentech; Honoraria (institution): Ipsen; Honoraria (institution): Ignyta; Honoraria (institution): Innate Pharma; Honoraria (institution): Loxo; Honoraria (institution): MedImmune; Honoraria (institution): Sanofi-Aventis. H.T. Landsteiner: Full / Part-time employment: Boehringer Ingelheim . G. Jayadeva: Full / Part-time employment: Boehringer Ingelheim. J. Alt: Advisory / Consultancy, Consulting fee: Boehringer Ingelheim.

BACKGROUND The cancer-cell-killing property of atezolizumab may be enhanced by the blockade of vascular endothelial growth factor-mediated immunosuppression with bevacizumab. This open-label, phase 3 study evaluated atezolizumab plus bevacizumab plus chemotherapy in patients with metastatic nonsquamous non-small-cell lung cancer (NSCLC) who had not previously received chemotherapy. METHODS We randomly assigned patients to receive atezolizumab plus carboplatin plus paclitaxel (ACP), bevacizumab plus carboplatin plus paclitaxel (BCP), or atezolizumab plus BCP (ABCP) every 3 weeks for four or six cycles, followed by maintenance therapy with atezolizumab, bevacizumab, or both. The two primary end points were investigator-assessed progression-free survival both among patients in the intention-to-treat population who had a wild-type genotype (WT population; patients with EGFR or ALK genetic alterations were excluded) and among patients in the WT population who had high expression of an effector T-cell (Teff) gene signature in the tumor (Teff-high WT population) and overall survival in the WT population. The ABCP group was compared with the BCP group before the ACP group was compared with the BCP group. RESULTS In the WT population, 356 patients were assigned to the ABCP group, and 336 to the BCP group. The median progression-free survival was longer in the ABCP group than in the BCP group (8.3 months vs. 6.8 months; hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.52 to 0.74; P<0.001); the corresponding values in the Teff-high WT population were 11.3 months and 6.8 months (hazard ratio, 0.51 [95% CI, 0.38 to 0.68]; P<0.001). Progression-free survival was also longer in the ABCP group than in the BCP group in the entire intention-to-treat population (including those with EGFR or ALK genetic alterations) and among patients with low or negative programmed death ligand 1 (PD-L1) expression, those with low Teff gene-signature expression, and those with liver metastases. Median overall survival among the patients in the WT population was longer in the ABCP group than in the BCP group (19.2 months vs. 14.7 months; hazard ratio for death, 0.78; 95% CI, 0.64 to 0.96; P = 0.02). The safety profile of ABCP was consistent with previously reported safety risks of the individual medicines. CONCLUSIONS The addition of atezolizumab to bevacizumab plus chemotherapy significantly improved progression-free survival and overall survival among patients with metastatic nonsquamous NSCLC, regardless of PD-L1 expression and EGFR or ALK genetic alteration status.