Article Text

Download PDFPDF

711 Interim results of a phase 2 study of nivolumab and relatlimab in advanced mismatch repair deficient (dMMR) cancers resistant to prior PD-(L)1 inhibition
  1. Katherine Bever,
  2. Hao Wang,
  3. Jennifer Durham,
  4. Colleen Apostol,
  5. Nilofer Azad,
  6. Ilene Browner,
  7. Stephanie Gaillard,
  8. Daniel Laheru,
  9. Valerie Lee,
  10. William Sharfman,
  11. Mark Yarchoan,
  12. Qingfeng Zhu,
  13. Robert Anders,
  14. Andrew Pardoll,
  15. Suzanne Topalian,
  16. Nicolas Llosa,
  17. Elizabeth Jaffee and
  18. Dung Le
  1. Johns Hopkins University, Baltimore, MD, USA


Background Cancers deficient in DNA mismatch repair (dMMR) are highly immunogenic but exhibit variable benefit from immune checkpoint inhibitors targeting programmed cell death-1 (PD-1)/PD-1 ligand (PD-L1). Other immune checkpoints are upregulated in these tumors and may be acting in parallel, in particular, lymphocyte activation gene 3 (LAG-3) which mediates exhaustion of activated T cells. The clinical relevance of the LAG-3 pathway has recently been demonstrated in 1L advanced melanoma (Tawbi NEJM 2022). We hypothesized that the addition of a LAG-3 blocking antibody (relatlimab) to a PD-1i (nivolumab) may overcome resistance to PD-(L)1 blockade in advanced dMMR tumors.

Methods Patients with advanced dMMR cancers that progressed during or within 6 months of PD-(L)1 inhibitor-containing therapy and after at least 12 weeks of therapy, and met other eligibility criteria were enrolled. Patients were treated with relatlimab 160 mg + nivolumab 480 mg (Cohort 1) every 4 weeks until intolerance or progression. Biopsies were obtained at baseline and on-treatment. The primary endpoint of the study is objective response rate according to RECIST 1.1. The outcomes of patients enrolled on Cohort 1 as of April 2022 are reported herein.

Results 15 patients were enrolled on Cohort 1 between November 2018 and April 2022. Of 13 patients evaluable for response (median follow up=12.4 months), partial response by RECIST 1.1 was observed in 1 patient with small bowel adenocarcinoma at 17 months (response duration of 11+ months), and 1 patient with colorectal cancer achieved a complete response at 18 months. An additional 5 patients achieved a best response of stable disease (SD), including one patient with 24% reduction in SLD ongoing at 41+ months. Treatment related adverse events (trAEs) occurred in 6 patients (40%) and were all G1-2 in severity. One patient discontinued treatment due to trAE (G2 oral pain/mucositis). Updated results will be presented at the time of the conference.

Conclusions Relatlimab + nivolumab is well tolerated and results in response or prolonged disease stability in some patients with advanced dMMR cancers that progressed on anti-PD-(L)1 therapy. Correlative analysis is ongoing to evaluate markers predictive of clinical benefit.

Acknowledgements Funding for this study was obtained through a grant from Bristol Myers Squibb. We gratefully acknowledge the patients who participated in this study and their families.

Trial Registration Clinical trial information: NCT03607890.

Ethics Approval This study was approved by the Johns Hopkins Medicine Institutional Review Board (IRB00173534). Written informed consent was obtained from participants prior to their participation.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.