New challenges in the combination of radiotherapy and immunotherapy in non-small cell lung cancer

Table 2 Ongoing clinical trials of radiotherapy and immune checkpoint inhibitors combination in locally advanced stage non-small-cell lung cancer in the neoadjuvant setting

Ref.	Phase	Design	No.ofpatients	Tumor stage	RT	ICI agent	Sequence	Status
CASE4516, NCT02987998[72]	1	Neoadjuvant CRT (CDDP-etoposide) + ICI followed by surgery and consolidative ICI	20	Resectable IIIA	45 Gy/25 fx (1.8 Gy/fx)	Pembroli zumab	Concomitant (neoadjuvant) + adjuvant ICI	Active, not recruiting
NCT03237377[73]	2	Neoadjuvant RT-ICI followed by surgery +/-adjuvant CT	32	Resectable IIIA	45 Gy/25 fx (1.8-2 Gy/fx)	Durvalumab ± tremelimumab	Concomitant(neoadjuvant)	Recruiting
NCT04245514, SAKK 16/18[74]	2 3 RT arms	Neoadjuvant RT-ICI followed by surgery	90	Resectable IIIA	Randomized 1:1:1; A: 20 × 2 Gy; B: 5 × 5 Gy; C: 3 × 8 Gy (non -consecutive days)	Durvalumab	Concomitant (neoadjuvant)	Recruiting
INCREASE, NL8435[75]	2 single arm	Neoadjuvant CRT (platinum doublet) + ICI followed by surgery	29	Resectable IIB-III (T3-4 N0-1)	50 Gy/25 fx	Ipilimumab + Nivolumab	Concomitant (neoadjuvant)	Recruiting
NCT02904954[76]	2 randomized	Neoadjuvant ICI +/- SBRT followed by surgery and adjuvant maintenance ICI	60	Resectable I-IIIA	SBRT 24 Gy/3 fx	Durvalumab	Concomitantneoadjuvant + adjuvant ICI	Active, not recruiting
NCT03871153[77]	2 single arm	Neoadjuvant CRT (Carbo-taxol) + ICI followed by surgery and adjuvant ICI	25	Resectable IIIA N2	45-61.2 Gy (25-34 fx a 1.8-2 Gy/fx)	Durvalumab	Concomitant (neoadjuvant) + adjuvant ICI	Recruiting
CHIO3, NCT04062708[78]	2single arm	Concomitant neoadjuvant CT (platinum doublet + ICI followed by surgery + adjuvant RT followed by ICI	55	Resectable IIIA-IIIB	54 Gy	Durvalumab	Concomitant CT-ICI (neoadjuvant) + adjuvant ICI (after adjuvant RT)	Not yet recruiting
NCT03102242[79]	2singlearm	Induction ICI followed by definitive CRT (Carbo-Taxol followed by consolidation CT-ICI	63	Unresectable IIIA-IIIB	60 Gy/30 fx	Atezolizumab	Neoadjuvant + consolidative ICI	Active, notrecruiting
NCT02572843[80]	2	Neoadjuvant CT (platinum + docetaxel) + ICI followed by surgery +/-RT + ICI	68	Resectable IIIA N2	Convenional RT if R1-R2 and before adjuvant ICI	Durvalumab	Neoadjuvant + adjuvant	Active, not recruiting

RT: Radiotherapy; CRT: Chemoradiotherapy; CT: Chemotherapy; ICI: Immune checkpoint inhibitor; Gy: Gray.