ODAC Votes 8-5 in Favor of Dostarlimab Trial in Advanced Rectal Cancer

An 8 to 5 vote was cast by the FDA’s Oncologic Drugs Advisory Committee (ODAC) in favor of a trial characterizing dostarlimab-gxly injection (Jemperli) as a single-agent for patients with locally advanced, treatment-naïve, mismatch repair deficiency (dMMR)/microsatellite instability–high (MSI-H) rectal cancer.¹

The committee was asked whether data from a proposed, single arm trial that will include 130 patients would be sufficient to identify the benefits and risks of dostarlimab with the intent of cure in patients with dMMR/MSI-H locally advanced rectal cancer.

The ODAC also discussed the adequacy of study 19288 (NCT04165772) including dostarlimab’s risk/benefit profile in the aforementioned population, study design, end points, and follow-up, as well as whether the data from the study are robust enough to allow for assessment.

Results from the study were previously presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, and the study 219369.²

“While the proposed study certainly won't answer all of our questions about the optimal use of immunotherapy in MSI-H locally advanced rectal cancer, I think they'll provide additional data to determine whether the initial pilot results are generalizable given the multi-institutional, multi-national nature of the proposed study—the longer follow-up and increased sample size,” according to Kristen Ciombor, MD, MSCI, an associate professor of medicine of the Division of Hematology and Oncology at Vanderbilt University, who voted in favor of the agent.

However, the vote was not unanimous and other committee members expressed hesitancy in casting a vote favoring the agent.

“I voted no because the question clearly [asked] whether the data are sufficient and I don't believe [they are],” according to Jorge A. Garcia, MD, a professor of Medicine and Urology at Case Western Reserve University School of Medicine. “I do believe this agent has great safety, efficacy, and a pretty impressive clinical complete response with the current data and I do believe this is a huge opportunity to delay or, for some, maybe never having to [risk] the morbidity of a surgical approach. However, I do not believe that the data that we have and the data that were proposed by the applicant are sufficient enough to characterize the benefits and risks in the curative setting in this patient population.”

The proposed approval pathway for dostarlimab is accelerated approval from the FDA. Dostarlimab was designed as a PD-1 inhibitor that blocks monoclonal antibodies.

The phase 2 study identified a complete response rate of 100% (95% CI, 74%-100%) in the 12 patients enrolled on the study. Additionally, investigators had not found any residual tumors when an MRI was conducted. At the time of the presentation, there were no cases of recurrence and no adverse effects higher than grade 3 were reported. Of note, the expansion of this trial will include 30 patients.

In August 2021, dostarlimab was approved in a new indication by the FDA for patients with dMMR recurrent or advanced solid tumors, as determined by an FDA-approved test, and who have progressed on or following prior treatment with no alternative options.³

The approval was based on the multi-cohort GARNET trial (NCT02715284), which enrolled 209 patients with dMMR advanced solid tumors.⁴ Of note, the objective response rate was 41.6% (95% CI, 34.9%-48.6%), 9.1% of which were complete responses and 32.5% were partial responses among those with endometrial tumors.

The FDA gave full approval to dostarlimab for dMMR endometrial cancer on February 9, 2023.⁵

References

1. February 9, 2023 Meeting of the Oncologic Drugs Advisory Committee (ODAC). Streamed live February 9, 2023. Accessed February 9, 2023. http://bit.ly/40Hqc65
2. Cercek A, Lumish M, Sinopoli J, et al. PD-1 Blockade in mismatch repair–deficient, locally advanced rectal cancer. N Engl J Med. 2022; 386(25):2363-2376. doi:10.1056/NEJMoa2201445
3. FDA grants accelerated approval to dostarlimab-gxly for dMMR advanced solid tumors. News release. FDA. August 17, 2021. Accessed February 9, 2023. https://bit.ly/3Yamdxf
4. Andre T, Berton D, Curigliano G, et al. Safety and efficacy of anti–PD-1 antibody dostarlimab in patients (pts) with mismatch repair-deficient (dMMR) solid cancers: Results from GARNET study. J Clin Oncol. 2021; 39(suppl_3):9. doi:10.1200/JCO.2021.39.3_suppl.9
5. FDA grants regular approval to dostarlimab-gxly for dMMR endometrial cancer. News release. FDA. February 9, 2023. Accessed February 9, 2023. http://bit.ly/3xbGuH2