Sugemalimab Study Highlights Notable Clinical Promise in Relapsed/Refractory ENKTL, Says Ranjit Nair, MD


Ranjit Nair, MD, discusses the promise of sugemalimab, both as a single-agent and as part of a combination regimen, in patients with relapsed/refractory extranodal natural killer/T-cell lymphoma.

Treatment with sugemalimab resulted in a promising overall survival (OS) benefit in patients with relapsed/refractory extranodal natural killer/T-cell lymphoma (ENKTL) and could lead to improved responses and even possibly cure in a difficult-to-treat population, according to Ranjit Nair, MD.

In the phase 2 GEMSTONE-201 trial (NCT03595657), a population of 80 patients who received the monotherapy experienced an overall response rate (ORR) by independent review committee of 46.2%, including a complete response (CR) rate of 37.2%. Moreover, 86.0% of patients maintained a response at 12 months. ORR by investigator assessment was 45.6% with a CR rate of 30.4%.

In an interview with CancerNetwork® during the 2022 American Society of Clinical Oncology Annual Meeting, Nair, an assistant professor in the Department of Lymphoma/Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, discussed the potential sugemalimab may have as part of a combination regimen in those with relapsed/refractory ENKTL.

CancerNetwork®: What was the rationale for assessing sugemalimab in patients with relapsed/refractory ENKTL?

Nair: Natural killer T-cell lymphoma is a rare subtype of peripheral T-cell lymphoma. It’s much more common in Asia and Latin America, but rare in North America. We probably see fewer than 200 cases per year in the United States. It’s such a rare disease that we don’t see a lot of dedicated trials for ENKTL because the patients get sick quickly once they have relapsed. This phase 2 study of sugemalimab in patients with relapsed/refractory ENKTL is a big undertaking.

This subtype of lymphoma is such a rare disease and it’s very treatable when you’re newly diagnosed. But almost half of the patients with advanced stage disease can relapse and a small group of patients with early-stage disease relapse too.

Once it relapses, the disease gets extremely challenging to treat and [the patients] tend to have chemotherapy-refractory disease. Some of the active agents for the treatment of this lymphoma includes asparaginase, and once patients [progress], the outcomes are very poor. We definitely need novel therapies, including immunotherapies, to address this. That’s where this study gets to be very relevant. This was a study that enrolled around 80 patients. This lymphoma tends to have an association with Epstein-Barr Virus [EBV]; about 80% to 90% of the patients with this subtype of lymphoma tend to have EBV-association, which tends to upregulate the PD-1/PD-L1 pathway. There are drugs that can target this pathway in this disease; sugemalimab targets this pathway. This was definitely a big proof-of-concept study in this disease subtype.

What kind of efficacy did sugemalimab yield in this patient population?

[This was] the pre-planned primary analysis of the phase 2 study, which is a multicenter study, for patients with ENKTL who relapsed after first-line of therapy. Sugemalimab—just to give some context about this drug—is a fully human, PD-L1–targeting monoclonal antibody. This is the largest registrational study for a drug targeting this pathway in ENKTL. The study is very important to move the needle forward. The primary analysis of the GEMSTONE-201 study had a primary end point of ORR by the independent radiology review committee and the secondary end points were CR rate, partial response rate, duration of response [DOR], and safety. So far, they have screened more than 120 patients and about 80 patients were enrolled. The median follow up was around 13.4 months. Just to give some demographics of the patients who were enrolled, the median age of the patients was 48 years. The majority of the patients were male—about 64%—and close to two-thirds of the patients had stage IV disease. Around [half of] patients had received 2 or more lines of therapy. The overall response rate was 46.2%. About 37.2% of patients achieved a CR. The median DOR was not reached at end of the pre-planned primary analysis.

What’s impressive about the study was that the 12-month median DOR was around 86%. At around a year, the majority of patients sustained remission which is quite impressive for a single agent in this highly chemotherapy refractory group of patients. The 1-year survival rate was 68.6% and the 2-year OS rate was 54.6%. The median OS was not reached at this primary analysis.

What stood out to you in terms of safety findings?

For most of the immune checkpoint inhibitors, we worry about immune-related adverse effects [IRAEs]. Most of the AEs that we worry about tend to be autoimmune. In summary, there were no major safety signals and there were no unforeseen complications with this drug. The majority of AEs were related to what we already know about this group of drugs. Most of the IRAEs were grade 1/2 and very manageable. The most common IRAE was hypothyroidism, which happened in about 16%. Outside of the IRAEs, the most common AEs tend to be fever and some degree of cytopenia, especially a decreased white blood cell count. It’s a well-tolerated drug overall.

What are the next steps for this research?

There’s definitely interest in using these novel agents in a combination. At this point, for patients who have relapsed/refractory ENKTL, I personally don’t think there is a cure outside of allogenic transplant. However, we do think these types of agents would be the optimal agents to combine with other drugs to improve the response rates and maybe even [achieve a] cure. It’s one of the big steps in that direction. But there are a lot of avenues for this drug to be explored in a combination.

What should your colleagues take away from this research?

Sugemalimab is currently available in United States [through] an expanded access program. There are patients with ENKTL who relapse after first- or second-line therapy, especially after asparaginase therapy. Immune checkpoint inhibitors are a very active [class of drug] for this group of patients. For centers that have this drug available in the expanded access, the patients can certainly reach out to these centers. We have this study as an expanded access program at MD Anderson Cancer Center, so we are a center that can provide this drug as part of the trial. Immune checkpoint inhibition should be explored further without any major AEs and seem to be much more tolerable.


Huang H, Tao R, Yang Y, et al. GEMSTONE-201: Preplanned primary analysis of a multicenter, single-arm, phase 2 study of sugemalimab (suge) in patients (pts) with relapsed or refractory extranodal natural killer/T cell lymphoma (R/R ENKTL). J Clin Oncol. 2022;40(16):7501. doi:10.1200/JCO.2022.40.16_suppl.7501

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