Immune-Checkpoint Inhibitors Combinations in Metastatic NSCLC: New Options on the Horizon?

Figures & data

Table 1 Main Ongoing Clinical Trials of Antiangiogenics Agents Combined with ICIs

Clinical Trial	Cancer Type	Treatment Line	Antiangiogenic Agent	Immunotherapy	Phase
NCT03377023	NSCLC	≥1	Nintedanib	Nivolumab + Ipilimumab	I/II
NCT03896074 (BEAT)	NSCLC	1	Bevacizumab	Atezolizumab Compared to: Atezolizumab	II
NCT03689855 (RamAtezo-1)	NSCLC	≥2	Ramucirumab	Atezolizumab	II
NCT03786692	EGFR+ NSCLC	>2	Bevacizumab	Atezolizumab + chemotherapy Compared to: Bevacizumab + chemotherapy	II
NCT03713944	Non-squamous NSCLC	1	Bevacizumab	Atezolizumab + chemotherapy	II
NCT03527108	NSCLC	≥2	Ramucirumab	Nivolumab	II
NCT02954991	NSCLC	≥2	Sitravatinib	Nivolumab	II
NCT03976375 (LEAP-008)	NSCLC	≥2	Lenvatinib	Pembrolizumab Compared to: Docetaxel Compared to: Lenvatinib monotherapy	III
NCT03829319 (LEAP-006)	Non-squamous NSCLC	1	Lenvatinib	Pembrolizumab + chemotherapy Compared to: Pembrolizumab + chemotherapy + placebo	III
WJOG11218L APPLE study	NSCLC	1	Bevacizumab	Atezolizumab + chemotherapy Compared to: Atezolizumab + chemotherapy	III

Abbreviation: NSCLC, non-small cell lung cancer.

Table 2 Main Ongoing Clinical Trials of Anti-LAG-3 Agents Combined with ICIs

Clinical Trial	Cancer Type	Treatment Line	Anti-LAG3 Agent	Immunotherapy	Phase
NCT03625323	NSCLC	≥1	Eftilagimod alfa	Pembrolizumab	II
NCT01968109	Advanced solid tumors	≥2	BMS-986,016	Nivolumab	Ib/II
NCT02460224	Advanced Malignancies	≥2	LAG525	PDR001 (anti-PD-1 mAb)	I/II
NCT03684785	Advanced solid tumors	≥2	Cavrotolimod	Pembrolizumab or cemiplimab	Ib/II
NCT03156114	Advanced solid tumors	≥2	BI 754,111	BI754091 (anti-PD-1 mAb)	I
NCT04140500	Advanced solid tumors	≥2	RO7247669 (anti-PD-1-LAG-3 Bispecific mAb)	-	I
NCT03849469	Advanced solid tumors	≥2	XmAb^®22,841	Pembrolizumab	I

Abbreviations: NSCLC, non-small cell lung cancer; mAb, monoclonal antibody.

Table 3 Main Ongoing Clinical Trials of Anti-Tim-3 Agents Combined with ICIs

Clinical Trial	Cancer Type	Treatment Line	Anti-Tim-3 Agent	Immunotherapy	Phase
NCT03099109	Advanced solid tumors	≥2	LY3321367	LY3300054 (anti-PD-L1 mAb)	I
NCT03307785	Advanced solid tumors	≥2	TSR-022	TSR-042 (anti-PD-L1 mAb)	I
NCT03311412	Advanced solid tumors and/or lymphomas	≥2	Sym023	Sym021 (anti-PD-1 mAb)	I
NCT02817633 (AMBER) Part 1 Part2 cohort B (NSCLC)	Advanced solid tumors	≥2	TSR-022	Nivolumab or TSR-042 (anti-PD-1 mAb)	I
NCT03708328	Advanced solid tumors	≥2	RO7121661 (anti-PD-1/TIM-3 bispecific mAb)	–	I
NCT03744468	Advanced solid tumors	≥2	BGB-A425	Tislelizumab (anti-PD-1 mAb)	I/II

Abbreviations: NSCLC, non-small cell lung cancer; mAb, monoclonal antibody.

Table 4 Main Ongoing Clinical Trials of Anti-TIGIT Agents Combined with ICIs

Clinical Trial	Cancer Type	Treatment Line	Anti-TIGIT Agent	Immunotherapy	Phase
NCT03119428	Advanced solid tumors	≥2	OMP-313M32	Nivolumab	I
NCT03628677	Advanced solid tumors	≥2	AB154	AB122 (anti-PD-1 mAb) Zimberelimab	I
NCT04294810 SKYSCRAPER-01	NSCLC	I	Tiragolumab	Atezolizumab Compared to: Placebo + Atezolizumab	III
NCT04513925 SKYSCRAPER-03	NSCLC (Stage III)	Consolidation after CRT	Tiragolumab	Atezolizumab Compared to: Durvalumab	III

Abbreviations: NSCLC, non-small cell lung cancer; mAb, monoclonal antibody; CRT, chemoradiation.

Table 5 Main Ongoing Clinical Trials of OX40 Agonistic Agents Combined with ICIs

Clinical Trial	Cancer Type	Treatment Line	OX40 Agonistic mAb	Immunotherapy	Phase
NCT02528357	Advanced solid tumors	≥2	GSK3174998	Pembrolizumab	I
NCT02410512	Advanced solid tumors	≥2	MOXR0916	Atezolizumab	Ib
NCT02554812	Advanced solid tumors	≥2	PF-04518600 (OX40 agonist mAb)	Avelumab	Ib/II
NCT02221960	Advanced solid tumors	≥2	MEDI6383 (recombinant human OX40L IgG4P Fc fusion protein)	Durvalumab	I
NCT03241173	Advanced Malignancies	≥2	INCAGN01949	Nivolumab or ipilimumab	I/II

Abbreviations: NSCLC, non-small cell lung cancer; mAb, monoclonal antibody.

Table 6 Main Ongoing Trials of PARPi Combined with ICIs

Trial	Cancer Type	Line of Treatment	PARP Inhibitor	Immunotherapy	Phase
UNITO–001	HRR-positive and PD-L1 ≥ 1% advanced NSCLC and/or MPM	≥2	Niraparib	TSR-042 (anti-PD-1 mAb)	II
NCT03307785	Advanced or metastatic cancer	≥1	Niraparib	TSR-042 (anti-PD-1 mAb)	I
NCT02484404	Advanced or metastatic cancer	N line	Olaparib	Durvalumab	I/II
NCT03559049	Non-squamous NSCLC	Maintenance	Rucaparib	Pembrolizumab	I/II
NCT03308942	NSCLC	1/2	Niraparib	Pembrolizumab/TSR-042 (anti-PD-1 mAb)	II
NCT03330405	NSCLC, TNBC, HR+ breast cancer, ovarian cancer, UC, CRPC.	≥1	Talazoparib	Avelumab	II
NCT03334617 (HUDSON)	NSCLC	≥2	Olaparib	Durvalumab	II
NCT03775486 (ORION)	NSCLC	Maintenance	Olaparib	Durvalumab Compared to: Durvalumab	II
NCT03976323 (KEYLYNK-006)	Non-squamous NSCLC	Maintenance	Olaparib	Pembrolizumab Compared to: Pembrolizumab + chemotherapy	III
NCT03976362 (KEYLYNK-008)	Squamous NSCLC	Maintenance	Olaparib	Pembrolizumab Compared to: Pembrolizumab + chemotherapy + placebo	III
NCT04380636 (KEYLYNK −012)	NSCLC	Maintenance	Olaparib	Pembrolizumab Compared to: Pembrolizumab + placebo Compared to: Durvalumab	III
NCT04173507 Lung-MAP	Non-squamous STK11-positive NSCLC	≥2	Talazoparib	Avelumab	II

Abbreviations: TNBC, triple-negative breast cancer; HR+, hormone receptor-positive; UC, urothelial cancer; CRPC, castration-resistant prostate cancer.

Table 7 Main Ongoing Trials of Cancer Vaccines Combined with ICIs

Trial	Cancer Type	Line of Treatment	Vaccine	Immunotherapy	Phase
NCT03380871	Non-squamous NSCLC	1	NEO-PV-01	Pembrolizumab + chemotherapy	I
NCT03647163	NSCLC	≥2	VSV-IFNβ-NIS	Pembrolizumab	I
NCT04266730	Squamous NSCLC, SCCHN	≥1	PANDA-VAC	Pembrolizumab	I
NCT03948763	NSCLC, CRC, Pancreatic Neoplasms	≥3	V941	Pembrolizumab	I
NCT03311334	Solid tumors	≥2	DSP-7888	Nivolumab	I/II
NCT02955290	NSCLC, SCCHN	≥2	CIMAvax	Nivolumab	I/II
NCT02879760	NSCLC	≥3	Ad-MAGEA3 and MG1-MAGEA3	Pembrolizumab	I/II
NCT02823990	Non-squamous NSCLC	≥2	TG4010	Nivolumab	II
NCT03353675	Non-squamous NSCLC	1	TG4010	Nivolumab + Chemotherapy	II

Abbreviations: CRC, colorectal cancer; SCCHN, squamous cell carcinoma of the head and neck.

Figure 1 Immune-checkpoint inhibitors combinations in non-oncogene addicted advanced NSCLC.