Table 1:

FDA approved immune checkpoint combinations

Combination	Control arm	Tumor type(s)	No of patients	Gd 3–5 toxicity	Median PFS (95% CI) (months)	Median OS (95% CI) (months)
Metastatic melanoma
Nivolumab 1mg/kg and Ipilimumab 3mg/kg (N+I) CHECKMATE067	Nivolumab 1mg/kg (N) Or Ipilimumab (3mg/kg) (I)	Metastatic melanoma: BRAF wildtype or mutant	945 (n = 314 in combination arm)	N+I: 60% N: 24% I: 28% †	N+I: 11.5 (8.7–19.3) N: 6.9 (5.1–10.2) I: 2.9 (2.8–3.2)	N+I: NR (38.2-NR) N: 36.9 (28.2–58.7) I: 19.9 (16.8–24.6) (8–11)
Atezolizumab, Cobimetinib, Vemurafenib (ACV) IMspire150	Cobimetinib, Vemurafenib, and Placebo (CV)	BRAF V600E-mutated advanced melanoma	514 (n=256 in ACV)	ACV 80% CV 73% †	ACV: 15.1 (11.4–18.4) CV: 10.6 (9.3–12.7)	NR 24-months: ACV: 60% CV: 53% (162)
Colorectal cancer
Nivolumab 3mg/kg and Ipilimumab 1mg/kg (N+I) CHECKMATE142	N/A	dMMR colorectal cancer, disease progression after 5FU, irinotecan or oxaliplatin based treatment	119	32%	NR 12 month PFS = 71% (61.4–78.7)	NR 12 month OS = 85% (77.0–90.2) (13)
Head and Neck Squamous Cell Cancer
Pembrolizumab and Chemotherapy (5-FU and platinum) (P + chemo) KEYNOTE-048	Cetuximab +chemotherapy (5-FU and platinum) (C + Chemo)	Untreated Recurrent or metastatic head and squamous cell cancer	ITT: 882 (n=281 for P + chemo; n=301 C + Chemo)	P + Chemo: 85% C + Chemo: 83%	P + Chemo: 4·9 (4·7−6·0) C + Chemo: 5·1 (4·9−6·0)	C + Chemo: 10.7 (9.3–11.7) P + Chemo: 13.0 (10.9–14.7)
			CPS ≥1: P + Chemo:242 C + Chemo: 235		P + Chemo: 5·0 (4·7−6·2) C + Chemo: 5·0 (4·8−5·8)	C + Chemo: 10.4 (9.1–11.7) P + chemo: 13.6 (10.7–15.5) (42)
Non-Small Cell Lung Cancer
Nivolumab 3mg/kg and Ipilimumab 1mg/kg (N+I) CHECKMATE-227	Nivolumab (N), Nivolumab + Platinum Doublet (N + Chemo) or Chemotherapy (chemo)	Stage IV or Recurrent NSCLC with WT EGFR and ALK	PD-L1% ≥ 1%: 1189 (n = 396 in N; n = 396 in N+I)	N+I: 36.8% N:19.9% Chemo:37.7 †	N+I: 5.1 (4.1–6.3) N: 4.2 (3.0–5.3) Chemo: 5.6 (4.6–5.8)	N+I: 17.1 (15.0–20.1) N: 15.7 (13.3–18.1) Chemo:14.9 (12.7–16.7)
			PD-L1% ≤ 1%: 550 (n=187 for N+I, n=177 for N+Chemo)	N+I:28.6% N+Chemo:58.1% Chemo:35.5% †	N+I: 5.1 (3.2–6.4) N+Chemo: 5.6 (4.6–6.9) Chemo: 4.7 (4.2–5.6)	N+I: 17.2 (12.8–22.0) N+Chemo: 15.2 (12.3–19.8) Chemo: 12.2 (9.2–14.3) (232)
Nivolumab 3mg/kg q 3w, Ipilimumab 1mg/kg q 6w + chemo (2 cycles) (IO) CHECKMATE-9LA	Chemotherapy – 4 cyles (Chemo)	Stage IV or recurrent NSCLC (EGFR/ALK non-mutated) – treatment naive	IO: 361 Chemo: 358	IO: 49% Chemo: 40% †	NE	IO: 15.6 (13.9–20.0) Chemo: 10.9 (9.5–12.5) (233)
Pembrolizumab, Pemetrexed and Platinum (PPP) KEYNOTE-189	Pemetrexed and platinum (Chemo)	Metastatic nonsquamous NSCLC (EGFR/ALK non-mutated)	616 (n = 410 in IO combination arm)	PPP: 71.9% Chemo: 66.8%	PPP: 9.0(8.1–9.9) Chemo: 4.9 (4.7–5.5)	PPP: 22.0 (19.5–25.2) Chemo: 10.7 (8.7–13.6) 24month OS = PPP: 45.5% Chemo: 29.9% (22,24)
Pembrolizumab, Chemotherapy (Carboplatin, Taxane) (PC) KEYNOTE-407	Carboplatin, Taxane (Chemo)	Metastatic squamous NSCLC	559 (n = 278 in IO combination arm)	PC: 74.1% Chemo: 69.6%	PC: 8.0 (6.3–8.4) Chemo: 5.1 (4.3–6.0)	PC: 17.1 (14.4–19.9) Chemo: 11.6 (10.1–13.7) (25,26)
Chemo-radiotherapy – durvalumab consolidation (IO) PACIFIC	Chemo-radiotherapy – placebo (Pl)	Stage III NSCLC	713 (n = 476 in IO combination arm)	IO: 34.9% Pl: 32.1% †	IO: 17.2 (13.1–23.9) Pl: 5.6 (4.6–7.7)	IO: NR (38.4-NR) Pl: 29.1 (22.1–35.1) 36-month OS: IO: 57.0 (52.3–61.4%) Pl:43.5% (37.0–49.9) (27–29)
Atezolizumab, Bevacizumab, Carboplatin, Paclitaxel (ABCP)* or Atezolizumab, Carboplatin, Paclitaxel (ACP) IMpower150	Bevacizumab, Carboplatin, Paclitaxel (BCP)	Metastatic non-squamous NSCLC (inc. EGFR/ALK mutated)**	Non-EGFR/ALK mutated 1045 (n = 359 in ABPC, n = 349 in ACP)	ACP: 43.8% ABCP: 58.5% BCP: 50.0% †	ABCP: 8.3 (7.7–9.8) BCP: 6.8 (6.0–7.1)	ABCP: 19.2 (17.0–23.8) BCP: 14.7 (13.3–16.9) (234,235)
			EGFR mutated 124 (n = 34 in ABCP and n = 45 in ACP)**		ABCP: 10.2 (7.9–15.2) BCP: 6.9 (5.7–8.5) ACP: 6.9 (5.7–8.2)	ABCP:NE (17.0-NE) BCP:18.7 (11.7-NE) ACP: 21.4 (13.8-NE)
Atezolizumab, Carboplatin, nab-paclitaxel (IO) IMpower130	Platinum-based chemotherapy (Chemo)	Metastatic non-squamous NSCLC (inc. EGFR/ALK mutated)$	Non-EGFR/ALK mutated 723 (n = 451 in IO, n = 228 in Chemo)	IO: 74.8% Chemo: 60.8%# †	IO: 7.0 (6.2–7.3) Chemo: 5.5 (4.4–5.9)	IO: 18.6 (16.0–21.2) Chemo: 13.9 (12.0–18.7) (236)
Extensive Stage Small Cell Lung Cancer (SCLC)
Atezolizumab, Carboplatin, Etoposide (APE) IMpower133	Carboplatin, Etoposide (Chemo)	Extensive Stage-SCLC	403 (n = 201 in IO combination arm)	APE: 69.2% Chemo: 64.8% †	APE: 5.2 (4.4–5.6) Chemo: 4.3 (4.2–4.5)	APE: 12.3 (10.8–15.8) Chemo: 10.3 (9.3–11.3) (32,33)
Durvalumab, Etoposide, Platinum (DPE) CASPIAN	Platinum Etoposide (chemo)	Extensive Stage -SCLC	805 (n = 268 for DPE)	DPE:66.4 % Chemo:68.0% †	DPE:5.1 (4.7–6.2) Chemo:5.4 (4.8–6.2)	DPE:13.0(11.5–14.8) Chemo: 10.3 (9.3–11.2) (34)
Triple negative breast cancer
Atezolizumab and nab-paclitaxel (AP) Impassion130	Nab-paclitaxel (Chemo)	Advanced triple negative breast cancer	ITT Population: 902 (n = 451 in IO combination arm)	AP: 50.1% Chemo: 43.0% †	AP: 7.2 (5.6–7.4) Chemo: 5.5 (5.3–5.6)	AP: 21.0 (19.0–22.6) Chemo: 17.5 (16.9–20.3)
			PD-L1 ≥ 1% 369 (n = 185 in IO combination arm)		AP: 7.5 (6.7–9.2) Chemo: 5.3 (3.8–5.6)	AP: 25.0 (19.6–30.7) Chemo: 18.0 (13.6–20.1) (39,127)
Renal cell cancer
Nivolumab 3mg/kg and Ipilimumab 1mg/kg (N+I) CHECKMATE 214	Sunitinib (S)	Metastatic clear cell renal cancer – int. - poor risk (IMDC score)	847 (n= 425 in combination arm)	N+I: 48% S: 65%	N+I: 8.2 (8.7–15.5) S: 8.3 (7.0–8.8)	N+I: NR (35.6-NR) S: 26.6 (22.1–33.4) 30 month OS = N+I: 60% (55–64%) S: 47% (43–52%)
		Metastatic clear cell renal cancer - favorable risk (IMDC score)	249 (n = 125 in combination arm)		N+I: 13.9 (9.9–17.9) S: 19.9 (15.1–23.5)	N+I: NR S: 32.9 (NE) 30 month OS = N+I: 80% (72–86-%) S: 85% (77–90%) (16,17)
Pembrolizumab, Axitinib (PA) KEYNOTE-426	Sunitinib (S)	Untreated Advanced Clear-Cell Renal Cell Carcinoma	861 (n = 432 in IO combination arm)	PA:75.8% S: 70.6%	PA: 15.4 (12.7–18.9) S: 11.1 (9.1–12.5)	mOS: PA: NR (NR-NR) S: 35.7 (33.3-NR) 24-month OS: PA: 74% S:66% (51,237)
Avelumab, Axitinib (A+A) JAVELIN RENAL 101	Sunitinib (S)	Untreated Renal Cell Carcinoma	Overall: 886 (n = 442 for IO combination)	A+A: 71.2% S: 71.5%	Overall Population: A+A: 13.3 (11.1–15.3) S: 8.0 (6.7–9.8)	NE
			PD-L1 ≥ 1% 560		PD-L1 Positive: A+A: 13.8 (10.1–20.7) S: 7.0 (5.7–9.6)	NE (52,238)
Hepatocellular cancer
Nivolumab 1mg/kg + Ipilimumab 3mg q 4w (A) Nivolumab 1mg/kg + Iipilimumab 3mg/kg q 3w (B) Nivolumab 3mg/kg q 2w + Ipilimumab 1mg/kg q 6w (C) CHECKMATE 040	none	Sorafenib treated advanced hepatocellular cancer	148 (n = 50 for A, n = 49 for B, n = 49 for C)	A: 53% B: 29% C: 31 %		A: 23 (9-NR) B: 12 (8–15) C:13 (7–33) (21)
Atezolizumab, Bevacizumab (AB)	Sorafenib (S)	Unresectable Hepatocellular Cancer	501 (n=336 in IO combination)	AB:61.1% S:60.9% †	AB: 6.8 (5.7–8.3) S:4.3 (4.0–5.6)	12-month OS: AB: 67.2%(61.3–73.1) S: 54.6% (45.2–64.0) (239)
Endometrial Cancer
Pembrolizumab, Lenvatinib	N/A	Advanced endometrial cancer (inc.MSI and MSS)&	108	68.5% †	Total: 7.4 (5.3–8.7) MSI: 18.9 (4.0-NE) MSS: 7.4 (5.0–7.6)	Total: 16.7 (15.0-NE) MSI: NE (7.4- NE) MSS: 16.4 (13.5–25.9) (44,45)

Notes:

NR = not reached

NE = not estimatable

IMDC score = International Metastatic Renal Cell Cancer Database Consortium score

MSI = Microsatellite instable

MSS = Microsatellite stable

^*Analysis of ACP vs. BCP has not yet been reported in NSCLC.

^**EGFR and ALK mutated non-squamous NSCLC are excluded from the FDA approval of ABCP.

^$EGFR and ALK mutated non-squamous NSCLC are excluded from the FDA approved of Atezolizumab, nab-paclitaxel and carboplatin.

^#Safety data includes EGFR and ALK mutated cancers.

^&FDA approval encompasses microsatellite stable cancers only.

^†- Grade 3–4 and Grade 5 reported sepearately in original paper, percentages calculated by combination of grade 3–4 and grade 5.