CONTACT-01: A Randomized Phase III Trial of Atezolizumab + Cabozantinib Versus Docetaxel for Metastatic Non-Small Cell Lung Cancer After a Checkpoint Inhibitor and Chemotherapy

Abstract

Purpose: Although checkpoint inhibitors have improved first-line treatment for non-small cell lung cancer (NSCLC), a therapeutic need remains for patients whose disease does not respond or who experience disease progression after anti-PD-L1/PD-1 immunotherapy. CONTACT-01 (ClinicalTrials.gov identifier: NCT04471428) evaluated atezolizumab plus cabozantinib versus docetaxel in patients with metastatic NSCLC who developed disease progression after concurrent or sequential treatment with anti-PD-L1/PD-1 and platinum-containing chemotherapy.

Methods: This multicenter, open-label, phase III trial randomly assigned patients 1:1 to atezolizumab 1,200 mg intravenously once every 3 weeks (q3w) plus cabozantinib 40 mg orally once daily or docetaxel 75 mg/m² intravenously once every 3 weeks. The primary end point was overall survival (OS).

Results: One hundred eighty-six patients were assigned atezolizumab plus cabozantinib, and 180 docetaxel. Minimum OS follow-up was 10.9 months. Median OS was 10.7 months (95% CI, 8.8 to 12.3) with atezolizumab plus cabozantinib and 10.5 months (95% CI, 8.6 to 13.0) with docetaxel (stratified hazard ratio [HR], 0.88 [95% CI, 0.68 to 1.16]; P = .3668). Median progression-free survival was 4.6 months (95% CI, 4.1 to 5.6) and 4.0 months (95% CI, 3.1 to 4.4), respectively (stratified HR, 0.74 [95% CI, 0.59 to 0.92]). Serious adverse events (AEs) occurred in 71 (38.4%) patients receiving atezolizumab plus cabozantinib and 58 (34.7%) receiving docetaxel. Grade 3/4 treatment-related AEs occurred in 73 (39.5%) patients receiving atezolizumab plus cabozantinib and 58 (34.7%) receiving docetaxel. Grade 5 AEs occurred in 14 (7.6%) and 10 (6.0%) patients in the atezolizumab plus cabozantinib and docetaxel arms, respectively (treatment-related in four [2.2%] and one [0.6%], respectively).

Conclusion: Atezolizumab plus cabozantinib after disease progression following anti-PD-L1/PD-1 immunotherapy and platinum-containing chemotherapy for metastatic NSCLC did not improve OS compared with docetaxel. Safety was consistent with known profiles of these agents.

FIG 1.

CONSORT diagram. Screened, randomly assigned, and treated patients, as well as analysis populations, are shown. AE, adverse event; ECOG PS, Eastern Cooperative Oncology Group performance status.

FIG 2.

OS. (A) Kaplan-Meier analysis of OS with atezolizumab plus cabozantinib versus docetaxel monotherapy in the intention-to-treat population. Stratified HR is reported. (B) Forest plot of OS by treatment arms in subgroups defined by patient baseline characteristics in the intention-to-treat population. Unstratified HRs are reported. ^aNot plotted because of small patient numbers: Black or African American (n = 3); Hispanic or Latino (n = 11); anti–PD-(L)1 monotherapy, then platinum added at PD (n = 2). ^bPer electronic case report form. ^cOnly includes patients with available or evaluable data. ^dSeven patients in the PD-L1 ≥1% category were excluded from evaluation in the PD-L1 1%-49% or ≥50% subsets, as the reported PD-L1 data from these patients did not enable these categorizations. CPI, checkpoint inhibitor; ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; NE, not estimable; NSCLC, non–small cell lung cancer; OS, overall survival; PD, progressive disease.

FIG 3.

PFS. Kaplan-Meier analysis of PFS with atezolizumab plus cabozantinib versus docetaxel monotherapy in the intention-to-treat population. Stratified HR is reported. HR, hazard ratio; PFS, progression-free survival.