Jemperli (dostarlimab-gxly) - 2 indications

Scroll down for information on each indication:

• for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer; approved April 2021
• for the treatment of adult patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumors; approved August 2021

General Information

Jemperli (dostarlimab-gxly) is a programmed death receptor-1 (PD-1)–blocking antibody.

Jemperli is specifically indicated for the following conditions:

• for treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer (EC), as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen
• for treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options

Jemperli is supplied as an injection for intravenous administration. The recommended dosage is:

• Dose 1 through Dose 4: 500 mg every 3 weeks
• Subsequent dosing beginning 3 weeks after Dose 4 (Dose 5 onwards): 1,000 mg every 6 weeks

Administer Jemperli as an intravenous infusion over 30 minutes. Treat patients until disease progression or unacceptable toxicity.

Mechanism of Action

Jemperli (dostarlimab-gxly) is a programmed death receptor-1 (PD-1)–blocking antibody. Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors, and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Dostarlimab-gxly is a humanized monoclonal antibody of the IgG4 isotype that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.

Side Effects

Adverse effects associated with the use of Jemperli may include, but are not limited to, the following:

• fatigue/asthenia
• nausea
• diarrhea
• anemia
• constipation

Indication 1 - for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer

approved April 2021

Clinical Trial Results

The FDA granted accelerated approval to Jemperli for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

The approval is based on results from the dMMR endometrial cancer cohort of the ongoing GARNET trial, a large, multicenter, non-randomized, multiple parallel-cohort, open-label study. Patients received 500 mg of Jemperli as an intravenous infusion once every three weeks for four doses, followed by 1,000 mg once every six weeks until disease progression or unacceptable toxicity.  The primary endpoints in the GARNET trial were overall response rate (ORR) and duration of response (DOR) as assessed by blinded independent central review (BICR). Results showed an ORR of 42.3% with a complete response (CR) rate of 12.7% and partial response rate (PR) of 29.6% among the 71 evaluable patients with dMMR advanced or recurrent endometrial cancer who had progressed on or after treatment with a platinum-containing regimen. Of those that responded, 93.3% demonstrated a DOR of 6 months or more. After a median follow-up of 14.1 months, the median duration of response was not reached (2.6-22.4+).

Indication 2 - for the treatment of adult patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumors

approved August 2021

Clinical Trial Results

The FDA granted accelerated approval to Jemperli for the treatment of adult patients with mismatch repair deficient (dMMR) solid tumors based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

FDA approval was based on the collective results from the dMMR endometrial cancer cohort A1 and the dMMR solid-tumor (non-endometrial cancer) cohort F of the ongoing GARNET trial. Cohort F included patients with dMMR recurrent or advanced non-endometrial cancers, with the highest prevalence in colorectal, small intestine and stomach cancers. The major efficacy outcomes of the GARNET trial are objective response rate (ORR) and duration of response (DoR), as assessed against RECIST v 1.1 by blinded independent central review. Results in all dMMR solid tumors, including endometrial and non-endometrial solid tumors (n=209), demonstrated an ORR of 41.6% with a complete response rate of 9.1% and a partial response rate of 32.5%. The median DoR was 34.7 months with 95.4% of patients maintaining a response for six months or longer. In the dMMR solid tumor non-endometrial cancer cohort (n=106), results demonstrated an ORR of 38.7%.