U.S. Food and Drug Administration (FDA)-Approved Indications

Jemperli is indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced:

Compendial Uses

Dostarlimab-gxly is available as Jemperli (GlaxoSmithKline) and is a programmed death receptor-1 (PD-1)-blocking lgG4 humanized monoclonal antibody. By binding PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor located on T cells, T-cell proliferation and cytokine production are inhibited (GlaxoSmithKline, 2021a).

Per the prescribing information, dostarlimab-gxly (Jemperli) carries the following warnings and precautions:

The most common adverse reactions (≥20%) are fatigue/asthenia, nausea, diarrhea, anemia, and constipation (GlaxoSmithKline, 2021a).

Endometrial Cancer

In the U.S., endometrial cancer (EC) is the most frequent gynecological malignancy with its prevalence on the rise. An estimated 75% of endometrial cancers are diagnosed at the beginning stage and are usually curable with surgery. Nevertheless, there are limited treatment options beyond front-line standard therapy with a platinum-containing chemotherapeutic regimen for women with advanced and recurrent endometrial cancer. Additionally, an estimated 25% to 30% of advanced endometrial cancer patients have mismatch repair deficient (dMMR) tumors (FDA, 2021a).

On April 22, 2021, the U.S. Food and Drug Administration (FDA) approved Jemperli (dostarlimab-gxly), a programmed death receptor-1 (PD-1) blocking antibody, indicated for the treatment of adult patients with mismatch repair-deficient (dMMR) recurrent or advanced endometrial cancer, as confirmed by an FDA-approved test, that have progressed on or following prior treatment with a platinum-containing regimen (GlaxoSmithKline, 2021a). The FDA granted Priority Review designation and Breakthrough Therapy designation to Jemperli for the endometrial cancer indication using the Accelerated Approval pathway (FDA, 2021a). The approval was based on supporting data from the ongoing GARNET study.

In the GARNET study, a multi-center, multicohort, open-label, non-randomized Phase 1 trial, Oaknin and colleagues (2020) evaluated the efficacy and safety of Jemperli in patients with dMMR endometrial cancer. Of the 104 enrolled women patients, the efficacy population consisted of 71 patients with dMMR recurrent or advanced EC who progressed on or after treatment with a platinum-containing regimen. Patients received 500 mg of Jemperli intravenously every 3 weeks for 4 doses followed by 1000 mg every 6 weeks until disease progression, treatment discontinuation, or withdrawal. The primary endpoints included objective response rate (ORR) and duration of response (DOR). Confirmed response was noted in 30 patients (objective response rate, 42.3%; 95% CI, 30.6%-54.6%); 9 patients (12.7%) had a confirmed complete response, and 21 patients (29.6%) had a confirmed partial response. The median duration of response was not reached (median follow-up was 11.2 months).The safety profile for Jemperli in patients included the occurrence of anemia (3 of 104 [2.9%]), colitis (2 of 104 [1.9%]), and diarrhea (2 of 104 [1.9%]) being the most common grade 3 or higher treatment-related adverse events.

Solid Tumors

On August 17, 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval to Jemperli (dostarlimab-gxly) for the 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. The approval was based on supporting data from the non-randomized, multicenter, open-label, multi-cohort GARNET study (FDA, 2021b).

In the GARNET study, the efficacy population comprised 209 patients with dMMR recurrent or advanced solid tumors who progressed following systemic therapy and had no satisfactory alternative treatment. Patients received Jemperli 500mg intravenously every 3 weeks for 4 doses followed by 1,000 mg intravenously every 6 weeks until disease progression or unacceptable toxicity. Primary efficacy endpoints included overall response rate (ORR) and duration of response (DOR). The results were as follows:41.6% (95% CI: 34.9, 48.6) for ORR, 9.1% for complete response rate, 32.5% for partial response rate, and 34.7 months (range 2.6, 35.8+) median DOR with 95.4% of patients with duration ≥ 6 months. The most common adverse reactions (≥20%) in these patients included fatigue/asthenia, anemia, diarrhea, and nausea. Commonly occurring Grade 3 or 4 reactions (≥2%) included anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury (FDA, 2021b).

: Requires Precertification:

Precertification of dostarlimab-gxly (Jemperli) is required of all Aetna participating providers and members in applicable plan designs. For precertification of dostarlimab-gxly (Jemperli), call (866) 752-7021 (Commercial), or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see

.

For Medicare Part B plans, call (866) 503-0857, or fax (844) 268-7263.

: Site of Care Utilization Management Policy applies. For information on site of service for

, see

.

Exclusions

Aetna will not provide coverage for members who have experienced disease progression while on PD-1 or PD-L1 inhibitor therapy.

Criteria for Initial Approval

Ampullary Adenocarcinoma

Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent for subsequent treatment of recurrent or advanced microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) ampullary adenocarcinoma that has progressed on or following prior treatment and has no satisfactory alternative treatment options.

Endometrial Carcinoma

Solid Tumors

Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent for treatment of mismatch repair deficient (dMMR) solid tumors in members with recurrent or advanced disease that have progressed on or following prior treatment and for whom there are no satisfactory alternative treatment options.

Breast Cancer

Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent for treatment of recurrent unresectable or stage IV breast cancer that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) and has progressed on or following prior treatment and has no satisfactory alternative treatment options.

Colorectal Cancer

Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent for treatment of advanced or metastatic colorectal cancer, including appendiceal adenocarcinoma, that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).

Esophageal, Esophagogastric Junction and Gastric Cancer

Aetna considers dostarlimab-gxly (Jemperli) medically necessary for treatment of esophageal, esophagogastric junction, or gastric carcinoma when

of the following criteria are met:

Occult Primary Cancer

Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent for treatment of occult primary cancer that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) and has progressed on or following prior treatment and has no satisfactory alternative treatment options.

Ovarian Cancer

Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent for treatment of epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer, carcinosarcoma (malignant mixed Mullerian tumors), clear cell carcinoma of the ovary, mucinous carcinoma of the ovary, grade 1 endometrioid carcinoma, and low-grade serous carcinoma/ovarian borderline epithelial tumors for recurrent, persistent, or advanced microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors.

Small Bowel Adenocarcinoma

Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent for treatment of advanced or metastatic small bowel adenocarcinoma for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors.

Aetna considers all other indications as experimental and investigational (for additional information, see Experimental and Investigational or Not Medically Necessary, and Background sections).

Continuation of Therapy

Aetna considers continuation of dostarlimab-gxly (Jemperli) therapy medically necessary in members requesting reauthorization for an indication listed in Section II when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Dosage and Administration

Dostarlimab-gxly (Jemperli) is available as 500 mg/10 mL (50 mg/mL) solution in a single-dose vial for intravenous infusion.

Endometrial Cancer and Solid Tumors

The recommended dosage of Jemperli is:

Source: GlaxoSmithKline, 2023