First-line immunotherapy with / without chemotherapy is standard of care for patients with advanced non-small-cell lung cancer ( NSCLC ); however, there is a need for effective treatment options after progression on a prior immune checkpoint inhibitor ( ICI ).
Cabozantinib ( Cabometyx ) may augment response to ICI by inhibiting kinases implicated in suppressing immune cell responses and has shown encouraging clinical activity in combination with immune checkpoint inhibitor in other tumor types including renal cell carcinoma ( RCC ) and hepatocellular carcinoma ( HCC ).
COSMIC-021, a multicenter phase 1b study, is evaluating the combination of Cabozantinib with Atezolizumab ( Tecentriq ) in various solid tumors.
Researchers have reported results from cohort 7 in NSCLC patients after prior ICI therapy.
Eligible patients had ECOG performance status ( PS ) 0-1 and radiographic progression after one prior anti-PD-1/PD-L1 ICI given alone or in combination with chemotherapy for metastatic non-squamous NSCLC.
Up to 2 lines of prior systemic anticancer therapies were permitted.
Patients received Cabozantinib 40 mg PO QD and Atezolizumab 1200 mg IV Q3W.
CT/MRI scans were performed Q6W for the first year and Q12W thereafter.
Primary endpoint was objective response rate ( ORR ) per RECIST 1.1 by investigator. Other endpoints have included safety, duration of response ( DOR ), progression-free survival ( PFS ), and overall survival ( OS ).
Thirty patients with advanced NSCLC were enrolled. Median age was 67 years ( range 41, 81 ), 43% were male, 57% had ECOG PS 1, and 23% had liver metastases.
Median duration of prior ICI therapy was 4.8 months ( range 0.8, 29 ), and 15 ( 50% ) patients were refractory to prior ICI ( progressive disease as best response ).
As of December 20, 2019, the median follow-up was 8.9 months ( range 5, 20 ) with 9 ( 30% ) patients continuing study treatment.
The most common treatment related adverse events ( TRAEs ) of any grade were diarrhea ( 53% ), fatigue ( 37% ), nausea ( 23% ), decreased appetite ( 20% ), palmar-plantar erythrodysesthesia ( 20% ) and vomiting ( 20% ).
Grade 3/4 TRAEs occurred in 14 ( 47% ) patients, and 1 ( 3.3% ) had grade 5 TRAEs of myocarditis and pneumonitis.
Confirmed ORR per RECIST 1.1 was 23% ( 7 of 30 patients; all partial responses including 3 patients refractory to prior ICI ).
Time to response was 1.4 months ( range 1, 3 ), and median DOR was 5.6 months ( range 2.6, 6.9 ).
Disease control rate ( DCR; CR+PR+SD ) was 83%.
In conclusion, the combination of Cabozantinib and Atezolumab had an acceptable safety profile and has shown encouraging clinical activity in patients with advanced non-small-cell lung cancer who had progressed after prior therapy with an immune checkpoint inhibitor.
The response rate was greater than previously observed with Cabozantinib monotherapy. ( Xagena )
Source: American Society of Clinical Oncology ( ASCO ) Virtual Meeting, 2020