Table 2 Clinical trials of the ICIs combination therapy

III

Nivolumab (PD-1) + Ipilimumab (CTLA-4)

nivolumab (at a dose of 1 mg/kg) plus ipilimumab (at a dose of 3 mg/kg) every 3 weeks for 4 doses followed by nivolumab (3 mg/kg every 2 weeks).

[n = 314]

/

11.5 m

Melanoma

NCT01844505

Active, not recruiting

^667,668

Nivolumab (PD-1)

nivolumab (at a dose of 3 mg/kg) every 2 weeks.

[n = 315]

/

6.9 m

Ipilimumab (CTLA-4)

ipilimumab(at a dose 3 mg/kg) every 3 weeks for 4 doses.

[n = 315]

/

2.9 m

II

Nivolumab (PD-1) + Ipilimumab (CTLA-4)

nivolumab (3 mg/kg, weeks 1 and 3) plus ipilimumab (1 mg/kg, given week 1 only) .

[n = 15]

/

/

OCSC

NCT02919683

Active, not recruiting

⁶⁷⁵

Nivolumab (PD-1)

nivolumab (3 mg/kg, weeks 1 and 3).

[n = 14]

/

/

II

Nivolumab (PD-1) + Ipilimumab (CTLA-4)

ipilimumab (3 mg/kg) plus nivolumab (1 mg/kg) once every 3 weeks for four doses, followed by nivolumab (3 mg/kg).

[n = 95]

63.8% (2-year OS rate)

51.3% (2-year PFS rate)

Melanoma

NCT01927419

Completed

⁶⁶⁹

Ipilimumab (CTLA-4)

ipilimumab (3 mg/kg) pluus placebo once every 3 weeks for four doses, followed by placebo.

[n = 47]

53.6% (2-year OS rate)

12% (2-year PFS rate)

II

Nivolumab (PD-1) + Ipilimumab (CTLA-4)

nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks.

[n = 119]

85% (1-year OS rate)

71% (1-year PFS rate)

MMR/MSI-H CRC

NCT02060188

Active, not recruiting

⁶⁷³

III

Nivolumab (PD-1) + Ipilimumab (CTLA-4)

nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) every 3 weeks for four doses, followed by nivolumab (3 mg/kg) every 2 weeks.

[n = 550]

75% (18-month OS rate)

11.6 m

RCC

NCT02231749

Active, not recruiting

⁶⁷⁰

Sunitinib (VEGFR2, PDGFRβ)

sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle).

[n = 546]

60% (18-month OS rate)

8.4 m

III

Nivolumab (PD-1) + Ipilimumab (CTLA-4)

nivolumab 3 mg/kg once every 2 weeks plus ipilimumab 1 mg/kg once every 6 weeks, nivolumab 240 mg once every 2 weeks alone.

[n = 583]

24% (5-years OS rate)

/

NSCLC

NCT02477826

Active, not recruiting

⁶⁷¹

Chemotherapy

platinum-doublet chemotherapy once every 3 weeks.

[n = 583]

14% (5-years OS rate)

/

III

Nivolumab (PD-1) + Ipilimumab (CTLA-4)

nivolumab (3 mg/kg every 2 weeks) plus ipilimumab (1 mg/kg every 6 weeks)

[n = 131]

/

/

ESCC

NCT03143153

Active, not recruiting

^676,677

Nivolumab (PD-1) + Chemotherapy

nivolumab (240 mg every 2 weeks) plus chemotherapy (4-week cycle of fluorouracil 800 mg/m² on days 1–5 and cisplatin 80 mg/m2 on day 1).

[n = 126]

/

/

Chemotherapy

chemotherapy (4-week cycle of fluorouracil 800 mg/m2 on days 1–5 and cisplatin 80 mg/m² on day 1).

[n = 137]

/

/

II

Nivolumab (PD-1) + Ipilimumab (CTLA-4) (pre-Chemotherapy)

nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg)

[n = 45]

19.0 m

5.5 m

Prostate Cancer

NCT02985957

Active, not recruiting

⁶⁷⁴

Nivolumab (PD-1) + Ipilimumab (CTLA-4) (post-Chemotherapy)

nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg)

[n = 45]

15.2 m

3.8 m

III

Nivolumab (PD-1) + Ipilimumab (CTLA-4)

nivolumab (3 mg/kg) every 2 weeks and ipilimumab (1 mg/kg) every 6 weeks.

[n = 303]

18.1 m

6.8 m

MPM

NCT02899299

Completed

^679,680

Chemotherapy

cisplatin (75 mg/m²) or carboplatin (500 mg/m²) plus pemetrexed in 3-week cycles for 6 cycles.

[n = 302]

14.1 m

7.2 m

II

Durvalumab (PD-L1) + Tremelimumab (CTLA-4)

durvalumab (20 mg/kg every 4 weeks) plus tremelimumab (1 mg/kg every 4 weeks) for 4 cycles, followed by durvalumab (10 mg/kg every 2 weeks).

[n = 21]

7.6 m

/

HNSCC

NCT02319044

Completed

⁶⁷²

Durvalumab (PD-L1)

durvalumab (10 mg/kg every 2 weeks) monotherapy.

[n = 8]

6.0 m

/

Tremelimumab (CTLA-4)

tremelimumab (10 mg/kg every 4 weeks for 7 doses then every 12 weeks for 2 doses) monotherapy.

[n = 11]

5.5 m

/

III

Durvalumab (PD-L1) + Tremelimumab (CTLA-4)

durvalumab (1500 mg) plus tremelimumab (75 mg) administered intravenously every 4 weeks for up to four doses, followed by durvalumab maintenance (1500 mg) every 4 weeks.

[n = 342]

15.1 m

/

Urothelial carcinoma

NCT02516241

Active, not recruiting

⁶⁷⁸

Durvalumab (PD-L1)

durvalumab monotherapy (1500 mg) administered intravenously every 4 weeks.

[n = 346]

14.4 m

/

Chemotherapy

gemcitabine plus cisplatin or gemcitabine plus carboplatin, depending on cisplatin eligibility administered intravenously for up to six cycles.

[n = 344]

12.1 m

/

II/III

Relatlimab (LAG-3) + Nivolumab (PD-1)

relatlimab (160 mg) plus nivolumab (480 mg) in a fixed-dose combination.

[n = 355]

/

10.1 m

Advanced Melanoma

NCT03470922

Active, not recruiting

⁶⁸⁶

Nivolumab (PD-1)

nivolumab (480 mg).

[n = 359]

/

4.6 m

II

Tiragolumab (TIGIT) + Atezolizumab (PD-L1)

tiragolumab (600 mg) plus atezolizumab (1200 mg) every 3 weeks.

[n = 67]

/

5.4 m

NSCLC

NCT03563716

Active, not recruiting

⁶⁹⁰

Atezolizumab (PD-L1)

atezolizumab (1200 mg) every 3 weeks.

[n = 68]

/

3.6 m

II

Nivolumab (PD-1) + Relatlimab (LAG-3) + Chemotherapy

nivolumab (360 mg) and relatlimab (120 mg) intravenously (IV) over 60 or 30 minutes, respectively, on days 1 and 22 of each 6-week treatment cycle. Oxaliplatin (130 mg/m²) was administered IV on days 1 and 22 of each cycle, and capecitabine(1,000 mg/m²) was administered orally twice daily on days 1-14 and days 22-35 of each cycle.

[n = 138]

13.5 m

7.0 m

Gastric cancer

NCT03662659

Completed

⁶⁹¹

Nivolumab(PD-1) + Chemotherapy

nivolumab (360 mg) administered intravenously (IV) over 60 or 30 minutes, respectively, on days 1 and 22 of each 6-week treatment cycle. Oxaliplatin 130 (mg/m²) was administered IV on days 1 and 22 of each cycle, and capecitabine 1,000 (mg/m²) was administered orally twice daily on days 1-14 and days 22-35 of each cycle.

[n = 136]

16.0 m

8.3 m