Phase 3
N=366
Study of Atezolizumab in Combination With Cabozantinib Versus Docetaxel in Patients With Metastatic Non-Small Cell Lung Cancer Previously Treated With an Anti-PD-L1/PD-1 Antibody and Platinum-Containing Chemotherapy
Carcinoma, Non-Small-Cell Lung
Bottom Line
View on ClinicalTrials.gov: NCT04471428 ↗Enrolled (actual)
366
Serious AEs
38.1%
Results posted
Dec 2023
Primary outcome: Primary: Overall Survival (OS) — 10.5; 10.7 months — p=0.3668
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Cabozantinib (Drug); Atezolizumab (Drug); Docetaxel (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Sep 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Survival (OS) |
10.5; 10.7 | 0.3668 |
| SECONDARY Progression-Free Survival (PFS) as Determined by Investigator |
4.0; 4.6 | 0.0079 sig |
| SECONDARY Confirmed Objective Response Rate (ORR) as Determined by Investigator |
13.3; 11.8 | 0.6846 |
| SECONDARY Duration of Response (DOR) as Determined by Investigator |
4.30; 5.55 | — |
| SECONDARY Time to Confirmed Deterioration (TTCD) in Patient-reported Physical Functioning (PF) |
5.6; 7.7 | 0.2700 |
| SECONDARY TTCD in Patient-reported Global Health Status (GHS) |
14.1; 8.1 | 0.2408 |
| SECONDARY PFS Rates Assessed by Investigator |
23.66; 39.51; 8.38; 14.70 | 0.0014 sig |
| SECONDARY OS Rates |
44.12; 43.27; NA; NA | 0.8767 |
| SECONDARY Percentage of Participants With Adverse Events (AEs) |
94.0; 98.4 | — |
| SECONDARY Minimum Serum Concentration (Cmin) of Atezolizumab |
NA; 96.8; 124; 167; 194; 233 | — |
| SECONDARY Maximum Serum Concentration (Cmax) of Atezolizumab |
450 | — |
| SECONDARY Minimum Plasma Concentration (Cmin) of Cabozantinib |
NA; 0.746; 0.418; 0.469; 0.303 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Cabozantinib |
— | — |
| SECONDARY Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab |
2; 37 | — |
Summary
This is a Phase III, multicenter, randomized, open-label study designed to evaluate the efficacy, safety, and pharmacokinetics of atezolizumab given in combination with cabozantinib compared with docetaxel monotherapy in patients with metastatic NSCLC, with no sensitizing EGFR mutation or ALK translocation, who have progressed following treatment with platinum-containing chemotherapy and anti-PD-L1/PD-1 antibody, administered concurrently or sequentially.
Eligibility Criteria
Inclusion Criteria
- Histologically or cytologically confirmed metastatic NSCLC
- Documented radiographic disease progression during or following treatment with platinum-containing chemotherapy and anti-PD-L1/PD-1 antibody, administered concurrently or sequentially for metastatic NSCLC
- Measurable disease per RECIST v1.1 outside CNS as assessed by investigator
- Known PD-L1 status or availability of tumor tissue for central PD-L1 testing
- ECOG Performance Status score of 0 or 1
- Recovery to baseline or Grade = 2 sensory or motor neuropathy
- Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, granulomatosis with polyangiitis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis with the following exceptions: Patients with a history of autoimmune-mediated hypothyroidism who are on thyroid replacement hormone are eligible for the study. Patients with controlled Type 1 diabetes mellitus are eligible for the study. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are eligible for the study provided all of following conditions are met: Rash must cover 480 ms per ECG within 14 days before initiation of study treatment
- Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic BP > 90 mm Hg despite optimal antihypertensive treatment
- Tumors invading the GI-tract, active peptic ulcer disease, acute pancreatitis, acute obstruction of the pancreatic or biliary duct, appendicitis, cholangitis, cholecystitis, diverticulitis, gastric outlet obstruction, or inflammatory bowel disease
- Abdominal fistula, bowel obstruction, GI perforation, or intra-abdominal abscess within 6 months before initiation of study treatment
- Known cavitating pulmonary lesion(s) or known endobronchial disease manifestation
- Lesions invading major pulmonary blood vessels
- Clinically significant hematuria, hematemesis, hemoptysis of > 0.5 teaspoon (2.5 mL) of red blood, coagulopathy, or other history of significant bleeding within 3 months before initiation of study treatment
- Serious non-healing wound/ulcer/bone fracture
- Malabsorption syndrome
- Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption are also excluded.
- Requirement for hemodialysis or peritoneal dialysis
- Inability to swallow tablets
Data sourced from ClinicalTrials.gov (NCT04471428). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.