Dostarlimab Shows Promise for Advanced Endometrial Cancer, Early Trial Results Show

Dostarlimab Shows Promise for Advanced Endometrial Cancer, Early Trial Results Show
4
(1)

A subset of women with recurrent or advanced endometrial cancer, whose disease progressed on or after platinum-based chemotherapy, achieved clinically meaningful responses after treatment with dostarlimab, results of a Phase 1 clinical trial show.

The findings, “Safety and efficacy of the anti–PD-1 monoclonal antibody dostarlimab in patients with recurrent or advanced dMMR endometrial cancer,” were presented in a webinar as part of the Society of Gynecologic Oncology’s 2020 virtual congress.

Dostarlimab (formerly known as TSR-042) is an immunotherapy developed by GlaxoSmithKline (GSK), which works by binding to a protein called PD-1 on the surface of cancer cells. This is intended to block binding of PD-1 to the PD-L1 and PD-L2 proteins on immune T-cells, a mechanism often used by tumors to avoid immune attack.

GARNET (NCT02715284) is an international assessment of dostarlimab as stand-alone therapy in patients with specific types of advanced solid tumors. The trial is still enrolling patients. For more information about contacts and locations, go here

The present data come from a group of 71 women whose endometrial cancer is mismatch repair-deficient (dMMR) — cells that carry mutations in genes normally involved in repairing DNA mistakes, increasing the risk of cancer. 

Patients with active or recurrent cancer were given four doses of 500 mg of dostarlimab once every three weeks, followed by 1,000 mg once every six weeks until disease progression. The median follow-up at data cutoff (July 8, 2019) was 11.2 months. 

Results showed that 42% of participants responded to treatment, including 13% with complete response — meaning total disappearance of cancer — and 30% with partial response.

Also, 59% of women showed stable disease. Duration of response had not been reached, which means that the overall study population was still responding to treatment. Among responders, 77% remained on treatment at data cutoff. 

“We are committed to developing medicines for patients who face high unmet medical need,” said Axel Hoos, MD, PhD, in a press release. Hoos is senior vice president and head of oncology research and development at GSK. “We believe in the clinical potential of dostarlimab for women with advanced or recurrent dMMR endometrial cancer,” he said.

Dostarlimab’s safety profile was evaluated in 104 patients who received at least one dose of the therapy. Dostarlimab was well-tolerated and only 2% of the patients discontinued the therapy due to treatment-related adverse events  (TRAEs) also seen in other anti-PD-1 therapies. (Adverse events are more commonly known as side effects.) The most common TRAEs were asthenia, or physical weakness (15%), diarrhea (15%), fatigue (14%), and nausea (13%). No dostarlimab-linked deaths were reported.

“The results observed in the GARNET trial indicate the potential of dostarlimab to offer a new treatment option for women with this challenging disease,” said Ana Oaknin, MD, head of the Gynaecologic Cancer Program at Vall d’Hebron Institute of Oncology, in Barcelona. She is a primary investigator for the GARNET trial.

Started in 2015, GARNET was designed as a two-part study. The first part focused on the safety and tolerability of dostarlimab to find the optimal dose for the second part, which tested the clinical activity of the therapy in five groups of patients with specific types of advanced solid tumors. 

Besides women with dMMR endometrial cancer, the trial includes participants whose endometrial cancer progressed on or after platinum double therapy, and also patients with dMMR non-endometrial cancers, non-small cell lung cancer, and platinum-resistant ovarian cancer.

Steve holds a PhD in Biochemistry from the Faculty of Medicine at the University of Toronto, Canada. He worked as a medical scientist for 18 years, within both industry and academia, where his research focused on the discovery of new medicines to treat inflammatory disorders and infectious diseases. Steve recently stepped away from the lab and into science communications, where he’s helping make medical science information more accessible for everyone.
Total Posts: 48
José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
×
Steve holds a PhD in Biochemistry from the Faculty of Medicine at the University of Toronto, Canada. He worked as a medical scientist for 18 years, within both industry and academia, where his research focused on the discovery of new medicines to treat inflammatory disorders and infectious diseases. Steve recently stepped away from the lab and into science communications, where he’s helping make medical science information more accessible for everyone.
Latest Posts
  • dostarlimab
  • Elenagen
  • Imfinzi, cancer spread

How useful was this post?

Click on a star to rate it!

Average rating 4 / 5. Vote count: 1

No votes so far! Be the first to rate this post.

As you found this post useful...

Follow us on social media!

We are sorry that this post was not useful for you!

Let us improve this post!

Tell us how we can improve this post?