Table 3.
Representative clinical trials evaluating the combination of PD-1/PD-L1 blockade immunotherapy and targeted therapy in EGFR-mutant NSCLC patients.
| Clinical trial # | PD-1/PD-L1 blockade therapy | Targeted therapy | Key findings | Reference |
|---|---|---|---|---|
| CheckMate 012 (NCT01454102) | Nivolumab | Erlotinib (EGFR TKI) |
- Phase I trial evaluating combination of nivoluman and various other agents including erlotinib - At least 4 out of the 20 recruited NSCLC patients with acquired resistance to EGFR TKI achieved clear benefit from combination of nivolumab and erlotinib (ORR = 15%, including 1 CR) |
(125) |
| NCT02013219 | Atezolizumab | Erlotinib (EGFR TKI) |
- Phase I trial in EGFR TKI-naïve and –treated NSCLC patients - Combination of atezolizumab and erlotinib was well tolerated and it exhibited favorable efficacy compared with prior reports of erlotinib monotherapy. ORR = 75% and median PFS = 15.4 months |
(126) |
| KEYNOTE-021 (NCT02039674) | Pembrolizumab | Gefitinib or erlotinib (EGFR TKI) |
- Phase I/II trial evaluating the combination of pembrolizumab with erlotinib or gefitinib in advanced NSCLC patients bearing EGFR mutation - Pembrolizumab plus erlotinib did not improve ORR compared with previous EGFR TKI monotherapy - Pembrolizumab plus gefitinib combination caused grade 3/4 liver toxicity in 5 out of 7 patients, resulting in premature treatment discontinuation |
(126) |
| NCT02088112 | Durvalumab | Gefitinib (EGFR TKI) |
- Open-label multicenter Phase I trial evaluating combination of gefitinib and durvalumab in patients with EGFR-mutant and EGFR TKI-naïve NSCLC - No significant improvement in PFS or ORR compared with gefitinib monotherapy previously reported in similar patient populations. - Gefitinib-naïve patients: ORR=63.6%; DoR=9.2 months; PFS=10.1 months - Gefitinib-pretreated patients: ORR=70.0%; DoR=12.6 months; PFS=12.0 months |
(127) |
| TATTON (NCT02143466) | Durvalumab | Osimertinib (EGFR TKI) |
- Phase Ib trial investigating the safety and tolerability of osimertinib and durvalumab combination - 38% of subjects developed serious interstitial pneumonitis |
(102) |
| IMpower150 (NCT02366143) | Atezolizumab | Bevacizumab (anti-VEGF monoclonal antibody) |
- Open-label Phase III study comparing atezolizumab + chemotherapy + bevacizumab (ABCP group) versus chemotherapy + bevacizumab (BCP group) in metastatic and chemotherapy-naïve NSCLC patients - ABCP group achieved significantly longer PFS (8.3 versus 6.8 months) and OS (19.2 versus 14.7 months) than BCP group, regardless of PD-L1 expression and EGFR/ALK genetic alteration status |
(128) |
CR, complete response; DoR, duration of response; ORR, objective response rate; OS, overall survival; PFS, progression free survival.