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Presidential Symposium II

LBA7 - Neoadjuvant immune checkpoint inhibition in locally advanced MMR-deficient colon cancer: The NICHE-2 study

Date

11 Sep 2022

Session

Presidential Symposium II

Topics

Immunotherapy;  Colon and Rectal Cancer

Presenters

Myriam Chalabi

Citation

Annals of Oncology (2022) 33 (suppl_7): S808-S869. 10.1016/annonc/annonc1089

Authors

M. Chalabi1, Y.L. Verschoor2, J. van den Berg3, K. Sikorska4, G. Beets5, A.V. Lent6, M.C. Grootscholten2, A. Aalbers5, N. Buller7, H. Marsman8, E. Hendriks9, P.W.A. Burger10, T. Aukema11, S. Oosterling12, R. Beets-Tan13, T.N. Schumacher14, M. van Leerdam2, E.E. Voest15, J.B.A.G. Haanen16

Author affiliations

  • 1 Gastrointestinal Oncology, Netherlands Cancer Institute, 1006 BE - Amsterdam/NL
  • 2 Gastrointestinal Oncology, NKI-AVL - Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 3 Pathology, NKI-AVL - Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 4 Biostatistics, Netherlands Cancer Institute, 1006 BE - Amsterdam/NL
  • 5 Surgical Oncology, NKI-AVL - Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 6 Gastroenterology And Hepatology, OLVG Hospital, 1091 HA - Amsterdam/NL
  • 7 Gastrointestinal Oncology, Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKI-AVL), 1066 CX - Amsterdam/NL
  • 8 Surgery, OLVG Hospital, 1091 HA - Amsterdam/NL
  • 9 Surgery, Tergooiziekenhuizen, 1261 AN - Blaricum/NL
  • 10 Surgery, Catharina Hospital Eindhoven, 5602 ZA - Eindhoven/NL
  • 11 Surgery, Hagaziekenhuis, 2547 EX - Den Haag/NL
  • 12 Surgery, Spaarne Hospital Hoofddorp, 2134TM - Hoofddorp/NL
  • 13 Radiology, Netherlands Cancer Institute, 1006 BE - Amsterdam/NL
  • 14 Molecular Oncology And Immunology, NKI-AVL - Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 15 Division Of Molecular Oncology And Immunology, NKI-AVL - Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 16 Medical Oncology, Netherlands Cancer Institute, 1066 CX - Amsterdam/NL
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Resources

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Abstract LBA7

Background

Neoadjuvant immunotherapy has shown promising responses in several cancer types. For colon cancer (CC), NICHE was the first neoadjuvant immunotherapy study to show pathologic responses in 100% of dMMR tumors. Importantly, disease-free survival (DFS) in patients (pts) with stage III dMMR CC is similar to that of pMMR pts, with 3-year recurrence risks of over 40% in high-risk (T4 and/or N2) stage III tumors despite adjuvant chemotherapy. Improving outcome for this patient population is urgently needed.

Methods

In the NICHE-2 study, pts with non-metastatic dMMR CC were treated with one dose of ipilimumab (1mg/kg) and two doses of nivolumab (3mg/kg) and underwent surgery ≤6 weeks of registration. The co-primary endpoints were safety (ITT) and 3-year DFS (PP). Secondary endpoints included major pathologic response (MPR) and complete response (pCR) rates. Pathologic response was defined as ≤50% residual viable tumor (RVT), and MPR as ≤10% RVT. Here we present safety and pathologic response data.

Results

A total of 112 pts were treated. Grade 3-4 immune-related adverse events were observed in 3 (3%) patients and only 3 pts experienced delay in surgery, meeting the safety primary endpoint. In the PP population (n=107), baseline radiologic assessment revealed 89% stage III, 77% high-risk stage III (Table), and 64% T4 tumors. With a median time from first dose to surgery of 5 weeks, pathologic response was observed in 106/107 (99%) pts, consisting of 102/107 (95%) MPR and 4 (4%) PR. PCR was observed in 72/107 (67%) pts. At a median follow-up of 13 months (range 1-57), none of the pts had disease recurrence. Table: 000LBA7

Pathologic response
MPR pCR
Clinical stage I/II (n = 12) 11 (92%) 9 (75%)
Low risk IIIa/b (n = 13) 13 (100%) 10 (77%)
High risk IIIa/b (n = 17) 16 (94%) 10 (59%)
High risk IIIc (n = 65) 62 (95%) 43 (66%)
Total (n = 107) 102 (95%) 72 (67%)

Conclusions

In NICHE-2 we confirm the previously reported pathologic responses to short-term neoadjuvant nivolumab plus ipilimumab in a large cohort of dMMR CC pts, with an MPR rate of 95%, including 67% pCR. The first survival data suggest a strong potential for neoadjuvant immunotherapy to become standard of care and allow further exploration of organ-sparing approaches.

Clinical trial identification

NL58483.031.16, EudraCT 016-002940-17.

Editorial acknowledgement

Legal entity responsible for the study

Netherlands Cancer Institute.

Funding

Bristol-Myers Squibb.

Disclosure

T.N. Schumacher: Financial Interests, Personal, Consultant: Third Rock Ventures; Financial Interests, Personal, Advisory Board: Allogene Therapeutics, Merus, Celsius Therapeutics; Financial Interests, Personal, Founder, Advisor: Asher Bio, Neogene Therapeutics; Financial Interests, Personal, Invited Speaker: Neogene Therapeutics; Financial Interests, Personal, Stocks/Shares: Third Rock Ventures, Allogene Therapeutics, Asher Bio, Merus, Neogene Therapeutics, Celsius Therapeutics. E.E. Voest: Financial Interests, Personal, Advisory Board, Hourly rate, to charity: Biogeneration Ventures; Financial Interests, Institutional, Advisory Board, Hourly rate, no compensation in 2019-2020: InteRNA; Financial Interests, Institutional, Invited Speaker, DRUP trial: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Clovis Oncology, Eisai, Ipsen, MSD, Novartis, Pfizer, GSK, Seattle Genetics; Financial Interests, Institutional, Invited Speaker, DRUP trial DRUG Access Protocol: Bayer, Roche; Financial Interests, Institutional, Invited Speaker, DRUG Access Protocol: Sanofi; Non-Financial Interests, Supervisory Board: HMF – Hartwig Medical Foundation; Non-Financial Interests, Principal Investigator, Senior Group Leader: Oncode Institute; Non-Financial Interests, Advisory Role, Editorial Board: JAMA Oncology; Non-Financial Interests, Leadership Role, Board of Directors: Cancer Core Europe. J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squipp, Achilles Therapeutics, Immunocore, Gadeta, Ipsen, Merck Sharpe & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Third Rock Venture, Iovance Biotherapeutics; Financial Interests, Institutional, Advisory Board, SAB member: BioNTech, Instil Bio, PokeAcel, T-Knife; Financial Interests, Personal, Advisory Board, SAB member: Neogene Therapeutics; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharpe & Dohme, Amgen, Novartis, Asher Bio; Non-Financial Interests, Member: ASCO, AACR, SITC; Editor-in-Chief IOTECH: ESMO, Editorial Board ESMO Open: ESMO; Editorial Board: Kidney Cancer. All other authors have declared no conflicts of interest.

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