Anti-PD-1/PD-L1 Therapy for Non-Small-Cell Lung Cancer: Toward Personalized Medicine and Combination Strategies

Table 3

Clinical trials of combination therapy with anti-PD-1/PD-L1 and targeted agents for NSCLC treatment.

PD-1/PD-L1 inhibitor	Targeted agent	Patients enrolled	Clinical setting(s)	Design and status	Phase	Clinical trial (NCT#)	Status	Estimated completion date
Pembrolizumab	Afatinib	38	Stage IIIA/IIIB/IV NSCLC (EGFR+) with resistance to erlotinib	Afatinib dimaleate (first) + pembrolizumab versus pembrolizumab (first) + afatinib dimaleate. Patients: recruiting participants.	I/Ib	NCT02364609	Recruiting	December 2018
Durvalumab	Gefitinib	56	NSCLC (EGFR+)	Durvalumab + gefitinib	I	NCT02088112	Active, not recruiting	June 14, 2019
Atezolizumab	Rociletinib (CO1686)	3	Advanced/metastatic NSCLC (EGFR+) regardless of T790M mutation	Rociletinib + atezolizumab	Ib/2	NCT02630186	Active, not recruiting	January 2017
Durvalumab	Osimertinib (AZD9291)	298	Advanced NSCLC (EGFR+)	AZD9291 + AZD6094 versus AZD9291 + continuous selumetinib versus AZD9291 + intermittent selumetinib versus AZD9291 + MEDI4736 versus AZD9291 + AZD6094 versus AZD9291 + selumetinib versus AZD6094 monotherapy (Japan only)	I	NCT02143466		December 28, 2018
Ipilimumab or nivolumab	Erlotinib or crizotinib	14	EGFR+ or ALK+ stage IV NSCLC	Erlotinib + erlotinib versus ipilimumab + crizotinib versus erlotinib + nivolumab versus crizotinib + nivolumab	I	NCT01998126	Active, not recruiting	December 2017
Atezolizumab	Erlotinib/alectinib	52	NSCLC (EGFR+ or ALK+)	Stage 1: alectinib + atezolizumab versus erlotinib + atezolizumab; Stage 2: alectinib + atezolizumab versus erlotinib + atezolizumab	Ib	NCT02013219	Active, not recruiting	December 1, 2018
Nivolumab	Crizotinib	78	NSCLC (ALK+)	Ceritinib + nivolumab	I	NCT02393625	Recruiting	October 2017
Pembrolizumab	Crizotinib	70	Advanced NSCLC (ALK+)	Crizotinib plus pembrolizumab	Ib	NCT02511184	Recruiting	September 2018
Nivolumab	Bevacizumab	472	Advanced NSCLC with response to platinum based chemotherapy	Nivolumab alone or +bevacizumab for maintenance treatment	I	NCT01454102	Recruiting	December 2018
Pembrolizumab	Ramucirumab	155	Solid tumor including NSCLC	Ramucirumab + pembrolizumab	Ia	NCT02443324	Active, not recruiting	August 2019
Pembrolizumab	Nintedanib	18	Solid tumor including NSCLC	Nintedanib + pembrolizumab	I	NCT02856425	Recruiting	July 2021

ALK: anaplastic lymphoma kinase; EGFR: epidermal growth factor receptor; NSCLC: non-small-cell lung cancer; PD-1: programmed death-1; PD-L1: programmed death-ligand 1. Information was summarized based on data published in https://www.clinicaltrials.gov/.