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Table 3 Important clinical trials of immunotherapy in dMMR CRC

From: Exploring immunotherapy in colorectal cancer

Clinical trial

NCT number

Phase

Status

Population

Arms and Interventions

Enrollment

ORR% (95% CI)

DCR% (95% CI)

PFS% (95% CI)

Significance

CheckMate-142

NCT02060188

2

Active, not recruiting

dMMR/MSI-H

[(Nivo 3 mg/kg + Ipi 1 mg/kg) Q3W] × 4 + (Nivo 3 mg/kg) Q2Wa

119

55 (45.2–63.8)

12w: 79 (70.6–85.9)

9 m: 76 (67.0–87.2); 12 m: 71 (61.4–78.7)

FDA accelerated the approval of Nivo + Ipi for the second-line treatment of dMMR mCRC

(Nivo 3 mg/kg) Q2Wa

74

31.1 (20.8–42.9)

12w: 68.9 (57.1%–79.2)

12 m: 50.4(38.1%–61.4)

FDA-approved Nivo for the second-line treatment of dMMR mCRC

(Nivo 3 mg/kg) Q2W + (Ipi 1 mg/kg) Q6Wb

45

69% (53–82)

 ≥ 12w 84 (70.5–93.5)

12 m: 76.4 (60.5–86.6), 18 m: 76.4 (60.5–86.6), 24 m: 73.6 (57.2–84.5)

Exploration of immunotherapy in the first-line treatment of advanced MSI CRC

Keynote-164

NCT02460198

2

Completed

dMMR/MSI-H

Cohort Ae

61

32.8 (21.3–46.0)h

50.8 (37.7–63.9)h

2.3 (2.1–8.1)d

Pemb was approved for MSI-H/dMMR mCRC patients after treatment progression with Fluorouracil, Oxaliplatin and Irinotecan

Cohort Be

63

34.9 (23.3–48.0)h

57.1 (44.0–69.5)h

4.1 (2.1–18.9)d

Keynote-016

NCT01876511

2

Completed

MSI

Cohort A:

Pemb 10 mg/kg Q2W

41 g

28 m: 54 (37–69)g

40 (12–74)f

28 m: 80 (65–91)g

90 (55–100)f

20w: 88 (75–100)

28w: 70 (57–86)g

Pemb was approved for the treatment of all solid tumors carrying MSI-H/dMMR

MSS

Cohort B:

Pemb 10 mg/kg Q2W

25 g

28 m: 0 (0–14)g

0 (0–19)f

28 m: 16 (5–36)g

11 (1–35)f

20w:12 (4–36)

28w: 16 (6–41)g

Keynote-177i

NCT02563002

3

Active, not recruiting

153 MSI

(Pemb 200 mg) Q3W

153

43.8% (35.8–52.0)

/

12 m: 55.3 (47.0–62.9)

24 m: 48.3 (39.9–56.2)

Pemb was approved by PDA for the first-line treatment of MSI mCRC

153 MSI

Chemotherapy Q2Wc

154

33.1% (25.8–41.1)

/

12 m: 37.3 (29.0–45.5)

24 m: 18.6 (12.1–26.3)

NICHE

NCT03026140

2

Recruiting

dMMR

Ipi (1 mg/kg) on D 1 + Nivo (3 mg/kg) on D1 and D156

20

100% (86–100%)

/

/

Exploration of immunotherapy in neoadjuvant therapy

pMMR

Ipi (1 mg/kg) on D 1 + Nivo (3 mg/kg) on D1 and D15 ± celecoxib from D1

15

26.7% (8–55%)

/

/

  1. Nivo Nivolumab, Ipi Ipilimumab, Pemb Pembrolizumab, D day, w Week, m Months
  2. aPatients must have progressed on/after or been intolerant of at least one prior line of treatment, including a fluoropyrimidine and oxaliplatin or irinotecan; patients who refused chemotherapy were permitted on protocol
  3. bPresented are results of nivolumab plus low-dose ipilimumab in the first-line therapy cohort from the phase II CheckMate-142 study
  4. cChemotherapy: 5-Fluorouracil based therapy ± Bevacizumab/Cetuximab
  5. dHere showed the result of median PFS (95% CI)
  6. eCohort A: Participants were previously treated with at least one line of systemic standard of care therapy: fluoropyrimidine + oxaliplatin or fluoropyrimidine + irinotecan ± anti vascular endothelial growth factor (VEGF)/ epidermal growth factor regulator (EGFR) monoclonal antibody
  7. Cohort B: Participants were previously treated with standard therapies, which must include fluoropyrimidine, oxaliplatin, and irinotecan
  8. fThe data are obtained from the article published on NEJM on June 25, 2015. At present, the final data have been updated
  9. gThe final results obtained from ClinicalTrials.gov
  10. hTime Frame: Up to approximately 4 years
  11. iUpdated information: the cutoff date of the data was February 19, 2021
  12. Pemb group: 36 m PFS1%: 42%; median-PFS1: 16.5 m (5.4–38.1); 12 m PFS2: 76%; 36 m PFS2: 60%; median-PFS2: 54.0 m (95% CI 44.4 m-NR) ORR: 45.1%
  13. Chem group: 36 m PFS1%: 11%; median-PFS1: 8.2 m (6.1–10.2); 12 m PFS2: 67%; 36 m PFS2: 39%; median-PFS2: 24.9 m (95% CI 16.6–32.6) ORR: 33.1%
  14. Pembro vs chemo met the prespecified criteria for PFS superiority at IA2. At final analysis, median PFS was 16.5 m vs 8.2 m (HR 0.59; 95% CI, 0.45–0.79), but did not meet statistical significance likely due to the high crossover rate from chemo to anti-PD1/PD-L1 therapies
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Journal of Hematology & Oncology

ISSN: 1756-8722

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