PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PRINCIPAL DISPLAY PANEL

NDC 0173-0898-03

Jemperli

(dostarlimab-gxly) Injection

500 mg/10 mL

(50 mg/mL)

gsk

For Intravenous Infusion after Dilution

Single-Dose Vial

Rx only

Dispense the enclosed Medication Guide to each patient

Rev. 3/23

PCR-0022923

![Jemperli 10 mL carton](/dailymed/image.cfm?name=jemperli-spl- graphic-04.jpg&id=880482)

RECENT MAJOR CHANGES SECTION

RECENT MAJOR CHANGES

Indications and Usage (1.1)	8/2024
Dosage and Administration (2.1, 2.2)	8/2024
Warnings and Precautions, Severe and Fatal Immune-Mediated Adverse Reactions (5.1)	3/2024

DOSAGE FORMS & STRENGTHS SECTION

Highlight: Injection: 500 mg/10 mL (50 mg/mL) solution in a single-dose vial. (3)

3 DOSAGE FORMS AND STRENGTHS

Injection: 500 mg/10 mL (50 mg/mL) clear to slightly opalescent, colorless to yellow solution in a single-dose vial for intravenous infusion after dilution.

CONTRAINDICATIONS SECTION

Highlight: None. (4)

4 CONTRAINDICATIONS

None.

CLINICAL STUDIES SECTION

14 CLINICAL STUDIES

14.1 Endometrial Cancer

In Combination with Carboplatin and Paclitaxel for the Treatment of Primary Advanced or Recurrent Endometrial Cancer

The efficacy of JEMPERLI in combination with carboplatin and paclitaxel, followed by JEMPERLI as a single agent, was evaluated in RUBY (NCT03981796), a randomized, multicenter, double-blind, placebo-controlled trial conducted in 494 patients with primary advanced or recurrent EC.

The trial enrolled patients with primary Stage III or Stage IV disease (per FIGO Staging Classification), including Stage IIIA to IIIC1 patients with evaluable or measurable disease, Stage IIIC1 patients with carcinosarcoma, clear cell, serous, or mixed histology regardless of presence of evaluable or measurable disease, Stage IIIC2 or Stage IV disease regardless of presence of evaluable or measurable disease. The trial also enrolled patients with first recurrent disease with a low potential for cure by radiation therapy or surgery alone or in combination, including patients who were naïve to systemic anticancer therapy or who had received prior neo-adjuvant/adjuvant systemic anticancer therapy and had a recurrence or disease progression ≥6 months after completing treatment.

Patients were randomized (1:1) to one of the following treatments arms:

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JEMPERLI 500 mg, carboplatin AUC 5 mg/mL/min, paclitaxel 175 mg/m2 intravenously on Day 1 of each 21-day cycle for 6 cycles followed by JEMPERLI 1,000 mg intravenously every 6 weeks. JEMPERLI was administered prior to chemotherapy on Day 1.

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Placebo, carboplatin AUC 5 mg/mL/min, paclitaxel 175 mg/m2 intravenously on Day 1 of each 21-day cycle for 6 cycles followed by placebo intravenously every 6 weeks.

Randomization was stratified by mismatch repair (MMR)/microsatellite instability (MSI) status, prior external pelvic radiotherapy, and disease status (recurrent, primary Stage III, or primary Stage IV). Treatment with JEMPERLI continued until disease progression, unacceptable toxicity, or a maximum of 3 years. Administration of JEMPERLI was permitted beyond disease progression (defined by Response Evaluation Criteria in Solid Tumors [RECIST] v1.1) if the patient was clinically stable and considered to be deriving clinical benefit by the investigator.

Assessment of tumor status was performed every 6 weeks through Week 25, every 9 weeks through Week 52 and every 12 weeks thereafter. The major efficacy outcomes were Progression-Free Survival (PFS) using RECIST v1.1 as assessed by investigator in the dMMR/MSI-H and overall populations, and Overall Survival (OS) in the overall population. Additional efficacy outcome measures included Objective Response Rate (ORR) per RECIST v1.1 as assessed by investigator and Duration of Response (DOR).

Among the 494 patients evaluated, the baseline characteristics were: median age 65 years (51% aged 65 years or older); 77% White, 12% Black, 3% Asian, 3% Hispanic or Latino; Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (63%) or 1 (37%); and primary stage III (18%); primary stage IV (34%) and recurrent EC (48%). Overall, 24% were dMMR/MSI-H tumors and 76% were mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumors.

Efficacy results are presented in Table 9 and Figures , and . Treatment with JEMPERLI in combination with carboplatin and paclitaxel demonstrated statistically significant improvements in OS in the overall population and PFS in both the dMMR/MSI-H and overall population versus placebo in combination with carboplatin and paclitaxel. Pre-specified exploratory analyses of PFS and OS were performed in patients with MMRp/MSS EC.

Table 9. Efficacy Results of Endometrial Cancer Population in RUBY

dMMR = Mismatch Repair Deficient; MSI-H = Microsatellite Instability-High; NR = Not Reached; + = ongoing at last assessment.
a Based on stratified Cox regression model.
b One-sided P-value based on stratified log-rank test.
c Confirmed responses.
Endpoint	Overall Population	dMMR/MSI-H Population
	JEMPERLI with Carboplatin and Paclitaxel N = 245	Placebo with Carboplatin and Paclitaxel N = 249	JEMPERLI with Carboplatin and Paclitaxel N = 60	Placebo withCarboplatin and Paclitaxel N = 62
Overall Survival (OS)
Number (%) of patients with event	109 (44)	144 (58)	15 (25)	35 (56)
Median in months (95% CI)	44.6 (32.6, NR)	28.2 (22.1, 35.6)	NR (NR, NR)	30.8 (18.7, NR)
Hazard ratio (95% CI)a	0.69 (0.54, 0.89)	0.34 (0.18, 0.62)
P-valueb	0.002	Not tested
Progression-Free Survival (PFS)
Number (%) of patients with event	135 (55)	177 (71)	23 (38)	47 (76)
Median in months (95% CI)	11.8 (9.6, 17.1)	7.9 (7.6, 9.5)	30.3 (11.8, NR)	7.7 (5.6, 9.7)
Hazard ratio (95% CI)a	0.64 (0.51, 0.80)	0.29 (0.17, 0.50)
P-valueb	<0.0001	<0.0001
Objective Response Rate (ORR)c
Number of participants with measurable disease at baseline (n)	172	185	42	45
ORR (95% CI)	68% (60, 75)	57% (50, 65)	74% (58, 86)	62% (47, 76)
Complete response rate	20%	12%	26%	11%
Partial response rate	48%	45%	48%	51%
Duration of Response (DOR)c

Median in months (range)	10.8 (1.3+, 28.9+)	6.4 (1.4+, 27.2+)	NR (3.4, 28.3+)	5.4 (2.7, 27.2+)

In patients with MMRp/MSS EC (n = 372), the OS hazard ratio (HR) was 0.82 (95% CI: 0.62, 1.08) with a median OS of 32.5 (95% CI: 28.6, NR) months for JEMPERLI in combination with carboplatin and paclitaxel versus 28.2 (95% CI: 21.9, 36.1) months for placebo in combination with carboplatin and paclitaxel. The PFS HR was 0.78 (95% CI: 0.60, 1.00) with a median PFS of 9.8 (95% CI: 9.0, 12.6) months for JEMPERLI in combination with carboplatin and paclitaxel (n = 185) versus 7.9 (95% CI: 7.6, 9.8) months for placebo in combination with carboplatin and paclitaxel (n = 187).

Figure 1. Kaplan-Meier Curve for Overall Survival in Patients (Overall Population) with Endometrial Cancer in RUBY

Figure 2. Kaplan-Meier Curve for Progression-Free Survival in Patients (Overall Population) with Endometrial Cancer in RUBY

Figure 3. Kaplan-Meier Curve for Progression-Free Survival in Patients with dMMR/MSI-H Endometrial Cancer in RUBY

dMMR = Mismatch Repair Deficient; MSI-H = Microsatellite Instability High.

As a Single Agent for the Treatment of dMMR Recurrent or Advanced Endometrial Cancer

The efficacy of JEMPERLI as a single agent was evaluated in the GARNET trial (NCT02715284), a multicenter, multicohort, open-label trial conducted in patients with advanced solid tumors. The efficacy population consisted of a cohort of 141 patients with dMMR recurrent or advanced EC who had progressed on or after treatment with a platinum‑containing regimen. Patients with prior treatment with PD‑1/PD‑L1–blocking antibodies or other immune checkpoint inhibitor therapy and patients with autoimmune disease that required systemic therapy with immunosuppressant agents within 2 years were excluded from the trial.

Patients received JEMPERLI 500 mg intravenously every 3 weeks for 4 doses followed by 1,000 mg intravenously every 6 weeks. Treatment continued until disease progression or unacceptable toxicity. The major efficacy outcome measures were ORR and DOR as assessed by blinded independent central review (BICR) according to the RECIST v 1.1.

The baseline characteristics were: median age 65 years (53% aged 65 years or older); 77% White, 4% Asian, 3% Black, 4% Hispanic or Latino; and Eastern Cooperative Oncology Group Performance Status 0 (38%) or 1 (62%).

The most common histology seen was endometrioid carcinoma type 1 (65%), Grade 3 endometrioid (15%), followed by serous (5%), mixed (5%) and undifferentiated (2.8%).

All patients with dMMR EC had received prior anticancer treatment, with 89% of patients receiving prior anticancer surgery and 71% receiving prior anticancer radiotherapy. Sixty-three percent of patients had one prior line of anticancer treatment and 37% had two or more prior lines. Forty-eight patients (34%) received treatment only in the neoadjuvant or adjuvant setting before participating in the study.

The dMMR tumor status was retrospectively confirmed using the VENTANA MMR RxDx Panel assay.

Efficacy results are presented in Table 10.

Table 9. Efficacy Results of dMMR Endometrial Cancer Population in GARNET

dMMR = Mismatch Repair Deficient; + = ongoing at last assessment. a Based on confirmed response by blinded independent central review.
b Median follow up for duration of response was 27.9 months measured from time of first response.
Endpoint	JEMPERLI N= 141
Overall response ratea
ORR (95% CI)	45.4% (37.0, 54.0)
Complete response rate	15.6%
Partial response rate	29.8%
Duration of responseb
Median in months	Not reached
(range)	(1.2+, 52.8+)
Patients with duration ≥12 months	85.9%
Patients with duration >24 months	54.7%

14.2 Mismatch Repair Deficient Recurrent or Advanced Solid Tumors

The efficacy of JEMPERLI as a single agent was evaluated in GARNET (NCT02715284), a non‑randomized, multicenter, open-label, multicohort trial. The efficacy population consisted of a cohort of 209 patients with dMMR recurrent or advanced solid tumors who progressed following systemic therapy and had no satisfactory alternative treatment options. Patients with dMMR EC must have progressed on or after treatment with a platinum-containing regimen. Patients with dMMR colorectal cancer must have progressed after or been intolerant to a fluoropyrimidine, oxaliplatin, and irinotecan.

Patients with prior treatment with PD‑1/PD‑L1–blocking antibodies or other immune checkpoint inhibitor therapy and patients with autoimmune disease that required systemic therapy with immunosuppressant agents within 2 years were excluded from the trial.

Patients received JEMPERLI 500 mg intravenously every 3 weeks for 4 doses followed by 1,000 mg intravenously every 6 weeks. Treatment continued until disease progression or unacceptable toxicity.

The major efficacy outcome measures were ORR and DOR as determined by a BICR according to RECIST v 1.1.

The baseline characteristics were female (77%); median age 63 years (47% aged 65 years or older); 63% White, 3% Asian, 2% Black; and Eastern Cooperative Oncology Group Performance Status 0 (39%) or 1 (61%).

At time of trial entry, 97.2% of patients (103/106) with non-endometrial dMMR solid tumors had Stage IV disease, and 68.0% (70/103) of patients with dMMR endometrial tumors had FIGO Stage IV disease.

Approximately 43% of patients had received 1 prior line of systemic anticancer treatment, 36% had received 2 prior lines, and 21% had received 3 or more prior lines.

The dMMR tumor status was retrospectively confirmed using the VENTANA MMR RxDx Panel assay.

Efficacy results are presented in Tables 11 and 12.

Table 10. Efficacy Results of dMMR Recurrent or Advanced Solid Tumors in GARNET

dMMR = Mismatch Repair Deficient; + = ongoing at last assessment. a Based on confirmed response by blinded independent central review.
b Median follow-up for duration of response was 17.5 months measured from time of first response.
Endpoint	JEMPERLI N= 209
Overall response ratea
ORR (95% CI)	41.6% (34.9, 48.6)
Complete response rate	9.1%
Partial response rate	32.5%
Duration of responseb
Median in months	34.7
(range)	2.6, 35.8+
Patients with duration ≥6 months	95.4%

Table 11. Efficacy Results of dMMR Tumor Types in GARNET

CR = complete response; CRC = colorectal cancer; dMMR = Mismatch Repair Deficient; DOR = Duration of Response; EC = endometrial cancer; ORR = Overall Response Rate; PD = progressive disease; PR = partial response; SD = stable disease; + = ongoing at last assessment.
a Exact, 2-sided 95% CI for binomial proportion.
Tumor Type	Patients N	ORR (per RECIST v 1.1)	DOR
n (%)	95% CIa	Range (months)
EC	103	46 (44.7)	(34.9, 54.8)	2.6, 35.8+
non-EC	106	41 (38.7)	(29.4, 48.6)	5.6, 30.1+
CRC	69	25 (36.2)	(25.0, 48.7)	5.6, 30.1+
Small intestinal cancer	12	4 (33.3)	(9.9, 65.1)	11.1+, 28.0+
Gastric cancers	8	3 (37.5)	(8.5, 75.5)	8.4+, 17.5
Pancreatic carcinoma	4	0 (0.0)	(0.0, 60.2)	NA
Biliary neoplasm	2	CR, CR	NA	8.4+, 13.5+
Liver cancer	2	PR, PD	NA	13.8+
Ovarian cancer	2	PR, SD	NA	25.1+
Adrenal cortical	1	PR	NA	19.5+
Breast cancer	1	CR	NA	16.8+
Esophageal cancer	1	PD	NA	NA
Genital neoplasm malignant female	1	PR	NA	22.2+
Pleural	1	PR	NA	15.2+
Renal cell carcinoma	1	SD	NA	NA
Unknown origin	1	PR	NA	20.4+

NONCLINICAL TOXICOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No studies have been performed to assess the potential of dostarlimab-gxly for carcinogenicity or genotoxicity.

Fertility studies have not been conducted with dostarlimab-gxly. In 1- and 3-month repeat‑dose toxicology studies in monkeys, there were no notable effects in the male and female reproductive organs; however, many animals in these studies were not sexually mature.

13.2 Animal Toxicology and/or Pharmacology

In animal models, inhibition of PD-L1/PD-1 signaling increased the severity of some infections and enhanced inflammatory responses. Mycobacterium tuberculosis-infected PD-1 knockout mice exhibit markedly decreased survival compared with wild-type controls, which correlated with increased bacterial proliferation and inflammatory responses in these animals. PD-1 blockade using a primate anti-PD-1 antibody was also shown to exacerbate M. tuberculosis infection in rhesus macaques. PD-L1 and PD-1 knockout mice and mice receiving PD-L1–blocking antibody have also shown decreased survival following infection with lymphocytic choriomeningitis virus.

SPL MEDGUIDE SECTION

MEDICATION GUIDE

JEMPERLI (jem-PER-lee)

(dostarlimab-gxly)

injection

What is the most important information I should know about JEMPERLI?

JEMPERLI is a medicine that may treat certain cancers by working with your immune system. JEMPERLI can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including:

Lung problems.

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cough

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shortness of breath

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chest pain

Intestinal problems.

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diarrhea or more bowel movements than usual

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stools that are black, tarry, sticky, or have blood or mucus

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severe stomach-area (abdomen) pain or tenderness

Liver problems.

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yellowing of your skin or the whites of your eyes

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severe nausea or vomiting

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pain on the right side of your stomach-area (abdomen)

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dark urine (tea colored)

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bleeding or bruising more easily than usual

Hormone gland problems.

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headaches that will not go away or unusual headaches

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eye sensitivity to light

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eye problems

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rapid heartbeat

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increased sweating

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extreme tiredness

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weight gain or weight loss

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feeling more hungry or thirsty than usual

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urinating more often than usual

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hair loss

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feeling cold

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constipation

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your voice gets deeper

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dizziness or fainting

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changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness

Kidney problems.

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change in the amount or color of your urine

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blood in your urine

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swelling in your ankles

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loss of appetite

Skin problems.

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rash

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itching

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skin blistering or peeling

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swollen lymph nodes

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painful sores or ulcers in your mouth or in your nose, throat, or genital area

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fever or flu-like symptoms

Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with JEMPERLI. Call or see your healthcare provider right away for any new or worse signs or symptoms.

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chest pain, irregular heartbeat, shortness of breath, swelling of ankles

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confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs

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double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight

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persistent or severe muscle pain or weakness, muscle cramps

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low red blood cells, bruising

**Infusion reactions that can sometimes be severe or life-threatening.**Signs and symptoms of infusion reactions may include:

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chills or shaking

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itching or rash

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flushing

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shortness of breath or wheezing

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dizziness

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feel like passing out

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fever

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back or neck pain

**Rejection of a transplanted organ.**Your healthcare provider should tell you what signs and symptoms you should report and monitor you, depending on the type of organ transplant that you have had.

**Complications, including graft-versus-host-disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic).**These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with JEMPERLI. Your healthcare provider will monitor you for these complications.

Getting medical treatment right away may help keep these problems from becoming more serious.

Your healthcare provider will check you for these problems during treatment with JEMPERLI. Your healthcare provider may treat you with corticosteroid or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with JEMPERLI, if you have severe side effects.

What is JEMPERLI?

JEMPERLI is a prescription medicine used to treat adults with:

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a kind of uterine cancer called endometrial cancer (EC)
○JEMPERLI may be used in combination with the chemotherapy medicines carboplatin and paclitaxel, and then after that, JEMPERLI may be used alone:

▪

when your cancer has spread outside your uterus (advanced)**or**,

▪

your cancer has returned.
○JEMPERLI may be used alone:

▪

when a laboratory test shows that your tumor is mismatch repair deficient (dMMR), and

▪

your cancer has returned, or it has spread (advanced EC), and

▪

you have received chemotherapy that contains platinum, and it did not work or is no longer working, and

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your cancer cannot be treated by surgery or radiation.

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a kind of cancer that is shown by laboratory test to be mismatch repair deficient (dMMR) solid tumor. JEMPERLI may be used alone to treat:
○cancer that has returned or has spread (advanced cancer) and,
○ has progressed during treatment or after treatment, and you have no satisfactory treatment options.

It is not known if JEMPERLI is safe and effective in children.

Before receiving JEMPERLI, tell your healthcare provider about all of your medical conditions, including if you:

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have immune system problems, such as Crohn’s disease, ulcerative colitis, or lupus.

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have received an organ transplant.

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have received or plan to receive a stem cell transplant that uses donor stem cells (allogeneic).

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have received radiation treatment to your chest area.

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have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome.

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are pregnant or plan to become pregnant. JEMPERLI can harm your unborn baby.
**Females who are able to become pregnant:**
○Your healthcare provider will do a pregnancy test before you start treatment with JEMPERLI.
○ You should use an effective method of birth control during your treatment and for 4 months after your last dose of JEMPERLI. Talk to your healthcare provider about birth control methods that you can use during this time.
○Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with JEMPERLI.

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are breastfeeding or plan to breastfeed. It is not known if JEMPERLI passes into your breast milk. Do not breastfeed during treatment and for 4 months after your last dose of JEMPERLI.

**Tell your healthcare provider about all the medicines you take,**including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How will I receive JEMPERLI?

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Your healthcare provider will give you JEMPERLI into your vein through an intravenous (IV) line over 30 minutes.

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When JEMPERLI is used in combination with carboplatin and paclitaxel, JEMPERLI is usually given every 3 weeks for the first 6 doses. Beginning 3 weeks later, it is usually given alone every 6 weeks.

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When JEMPERLI is used alone to treat dMMR recurrent or advanced EC and dMMR recurrent or advanced solid tumors, it is usually given every 3 weeks for the first 4 doses. Beginning 3 weeks later, it is usually given every 6 weeks.

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Your healthcare provider will decide how many treatments you need.

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Your healthcare provider will do blood tests to check you for side effects.

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If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.

What are the possible side effects of JEMPERLI?

JEMPERLI can cause serious side effects.

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**See “What is the most important information I should know about JEMPERLI?”**

The most common side effects of JEMPERLI when given with carboplatin and paclitaxel in people with EC include:

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nerve problems in your arms, hands, legs, and feet

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tiredness

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nausea

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hair loss

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joint pain

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rash

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constipation

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diarrhea

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stomach-area (abdomen) pain

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shortness of breath

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decreased appetite

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urinary tract infections

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vomiting

The most common side effects of JEMPERLI in people with dMMR solid tumors (including EC) when used alone include:

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tiredness and weakness

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low red blood cell count (anemia)

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diarrhea

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nausea

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constipation

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vomiting

These are not all of the possible side effects of JEMPERLI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of JEMPERLI.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. If you would like more information about JEMPERLI, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about JEMPERLI that is written for healthcare professionals.

What are the ingredients in JEMPERLI?

Active ingredient: dostarlimab-gxly

Inactive ingredients: citric acid monohydrate, L-arginine hydrochloride, polysorbate 80, sodium chloride, trisodium citrate dihydrate, and Water for Injection.

Trademarks are owned by or licensed to the GSK group of companies.

Manufactured by:

GlaxoSmithKline LLC, Philadelphia, PA 19104, U.S. License No. 1727

Distributed by:

GlaxoSmithKline, Durham, NC 27701

JMP:5MG

For more information, call 1-888-825-5249 or go to www.gsk.com.

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: August 2024

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