Dostarlimab for Advanced Cancer

(GARNET Trial)

Not currently recruiting at 141 trial locations

Overseen By EU GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Tesaro, Inc.

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Uncontrolled CNS metastases, Active autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, dostarlimab (an immunotherapy drug), for individuals with advanced solid tumors who have limited treatment options. The study is in its first phase, focusing on the safety of dostarlimab and how the body processes it. Different groups will receive varying doses to determine the safest and most effective one. Individuals with endometrial cancer, non-small cell lung cancer, and other specific advanced cancers may qualify if previous treatments have not succeeded. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants should not have received certain anti-cancer therapies or immunosuppressive treatments shortly before starting the trial. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that dostarlimab is likely to be safe for humans?

Research has shown that dostarlimab is generally safe for patients with advanced cancers. In earlier studies, patients using dostarlimab experienced positive outcomes, particularly those with certain types of endometrial cancer. The FDA has approved dostarlimab for use with chemotherapy in advanced or recurrent endometrial cancer, confirming its safety for humans. While side effects can occur with any treatment, dostarlimab has helped patients live longer. This information may reassure those considering participation in a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about dostarlimab for advanced cancer because it works by blocking a protein called PD-1, which can help the immune system better recognize and attack cancer cells. Unlike standard chemotherapy, which targets all rapidly dividing cells and can cause significant side effects, dostarlimab specifically enhances the body's immune response against cancer. This targeted approach may lead to fewer side effects and better outcomes for patients with certain types of advanced cancers, such as endometrial cancer and non-small cell lung cancer. Additionally, dostarlimab is administered as an intravenous infusion, offering a different mode of delivery compared to traditional oral or injection-based chemotherapy treatments.

What evidence suggests that dostarlimab could be an effective treatment for advanced cancer?

Research shows that dostarlimab holds promise for treating several advanced cancers. In this trial, participants with endometrial cancer, particularly those with mismatch repair deficiencies (dMMR), will receive dostarlimab, which has been linked to longer survival compared to other treatments. Studies have found that combining dostarlimab with chemotherapy helps patients with advanced endometrial cancer live longer without disease progression. Participants with non-small cell lung cancer (NSCLC) will also receive dostarlimab, which performs as well as other leading treatments when combined with chemotherapy. For other cancers with dMMR or high microsatellite instability (MSI-H), early research suggests that dostarlimab can significantly shrink tumors or slow their growth. ^{2 6 7 8 9}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

Adults with advanced solid tumors and limited treatment options can join this trial. They must have specific tumor types, adequate organ function, and an ECOG performance status of <=2 for Part 1 or <=1 for Part 2. Women must not be pregnant and agree to use contraception. Participants cannot have had more than three prior cancer therapies.

Inclusion Criteria

My condition worsened after platinum-based chemotherapy.

I've had up to 2 cancer treatments for my advanced disease, not counting hormone therapy.

My tumor's MMR/MSI status was checked and is eligible for the trial.

Exclusion Criteria

Participant has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, might interfere with the participant's participation for the full duration of the study treatment, or is not in the best interest of the participant to participate.

I have been treated with a PARP inhibitor before.

I have been treated with drugs targeting the PD-1 or PD-L1/L2 pathways.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Safety evaluation, pharmacokinetics (PK), and pharmacodynamics (PDy) of escalating doses of dostarlimab

Up to 2 years

Visits on Day 1 and Day 15 of each 28-day cycle

Cohort Expansion

Evaluation of safety and clinical activity of dostarlimab in specific cohorts with advanced solid tumors

Up to 2 years

Every 3 weeks or every 6 weeks depending on dosing schedule

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dostarlimab

Trial Overview The study tests dostarlimab (TSR-042), a drug targeting the PD-1 receptor in two parts: dose escalation to find the maximum tolerated dose, then fixed-dose safety evaluation and expansion cohorts focusing on specific tumor types to assess safety and clinical activity.

How Is the Trial Designed?

Group I: Part 2B:Cohort F non-endometrial dMMR/MSI-H & POLE-Mut cancers Experimental Treatment 1 Intervention

Participants with recurrent or advanced dMMR/MSI-H solid tumors except endometrial cancers, and gastrointestinal cancers, who have received prior systemic therapy and, who have no alternative treatment options. These participants will receive dostarlimab 500 mg for Q3W for the first 4 cycles followed by 1000 mg Q6W for all subsequent cycles.

Group II: Part 2B: Cohort G PROC without known BRCA Experimental Treatment 1 Intervention

Participants with advanced, relapsed, high-grade serous, endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal cancer without known breast cancer susceptibility gene (BRCA) mutation who have platinum-resistant disease receiving dostarlimab and who have also been previously treated with bevacizumab. These participants will receive dostarlimab 500 mg for Q3W for the first 4 cycles followed by 1000 mg Q6W for all subsequent cycles.

Group III: Part 2B: Cohort E NSCLC Experimental Treatment 1 Intervention

Part 2B: Cohort E NSCLC will include participants with non-small cell lung cancer (NSCLC) who progressed after at least 1 prior platinum-based systemic chemotherapy regimen for recurrent or advanced disease. These participants will receive dostarlimab 500 mg for Q3W for the first 4 cycles followed by 1000 mg Q6W for all subsequent cycles.

Group IV: Part 2B: Cohort A2 MMR-proficient/MSS endometrial cancer Experimental Treatment 1 Intervention

Part 2B: Cohort A2 will include participants with MMR-proficient/MSS endometrial cancer who have progressed on or after platinum doublet therapy. These participants will receive dostarlimab 500 mg for Q3W for the first 4 cycles followed by 1000 mg Q6W for all subsequent cycles. Participants have received no more than 2 lines of anti-cancer therapy for recurrent or advanced (Stage \>=IIIB) disease.

Group V: Part 2B: Cohort A1 dMMR/MSI-H endometrial cancer Experimental Treatment 1 Intervention

Part 2B: Cohort A1 will include participants with mismatch repair deficient microsatellite instability high (dMMR/MSI-H) endometrial cancer who have progressed on or after platinum doublet therapy. These participants will receive dostarlimab 500 mg for Q3W for the first 4 cycles followed by 1000 mg Q6W for all subsequent cycles. Participants have received no more than 2 lines of anti-cancer therapy for recurrent or advanced (Stage \>= IIIB) disease.

Group VI: Part 2A: Participants receiving dostarlimab Experimental Treatment 1 Intervention

In Part 2A, participants will receive fixed dose of 500 mg administered Q3W or 1000 mg administered Q6W dose on Day 1 of each cycle. Cycle duration for Q3W dosing is 21 days and Q6W dosing is 42 days. Cohorts will enroll participants with advanced solid tumor using a modified 6+6 design and will follow a 6+6 design.

Group VII: Part 1: Participants receiving dostarlimab Experimental Treatment 1 Intervention

Part 1 will evaluate dostarlimab at ascending weight-based doses 1 mg/kg, 3 mg/kg and 10 mg/kg. Higher dose levels 15 mg/kg and/or 20 mg/kg may also be explored. Dostarlimab will be administered intravenously (IV) on Day 1 and Day 15 of each cycle; cycle length is 28 days. Cohorts will be enrolled sequentially and will initially follow a 3+3 design.

Dostarlimab is already approved in European Union, United States for the following indications:

Approved in European Union as Jemperli for:

• Mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer
• dMMR/MSI-H recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen

Approved in United States as Jemperli for:

• Adults with dMMR recurrent or advanced solid tumors who have progressed on or following prior treatment and lack satisfactory alternative treatment options
• Primary advanced or recurrent dMMR endometrial cancer in combination with carboplatin and paclitaxel

Who Is Running the Clinical Trial?

Tesaro, Inc.

Lead Sponsor

Trials

57

Recruited

10,600+

Published Research Related to This Trial

Dostarlimab showed promising antitumor activity in patients with recurrent/advanced non-small cell lung cancer (NSCLC) who had progressed after platinum-based chemotherapy, achieving an immune-related objective response rate (irORR) of 26.9% across various PD-L1 expression levels.

The treatment was generally well-tolerated, with fatigue being the most common severe adverse event (4.5%), and immune-related treatment-emergent adverse events occurring in 28.4% of patients, indicating an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Dostarlimab in Patients With Recurrent/Advanced Non-small Cell Lung Cancer: Results from Cohort E of the Phase I GARNET Trial. Moreno, V., Roda, D., Pikiel, J., et al.[2023]

Dostarlimab, an anti-PD-1 monoclonal antibody, has been shown to be equipotent to pembrolizumab in suppressing PD-1 activity, with an estimated effective concentration of 1.95 μg/ml based on data from the GARNET trial.

The recommended dosing regimen for dostarlimab is 500 mg every 3 weeks for 4 cycles, followed by 1000 mg every 6 weeks, which supports its use as a potent treatment option for patients with recurrent or advanced mismatch repair-deficient solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative analysis of PD-1 target engagement of dostarlimab and pembrolizumab in advanced solid tumors using ex vivo IL-2 stimulation data. Austin, D., Melhem, M., Gandhi, Y., et al.[2023]

Dostarlimab (JEMPERLI) has been shown to effectively reduce tumor size in patients with certain types of endometrial cancer, as demonstrated in the ongoing GARNET phase 1 clinical study.

The treatment was associated with manageable side effects and few severe adverse reactions, leading to its approval for patients with advanced or recurrent endometrial cancer, where treatment options are limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A plain language summary of results from the GARNET study of dostarlimab in patients with endometrial cancer. Oaknin, A., Gilbert, L., Tinker, AV., et al.[2023]

Dostarlimab is a monoclonal antibody that targets the PD-1 receptor and has been approved for treating adult patients with mismatch repair deficient recurrent or advanced endometrial cancer based on promising results from the GARNET trial.

The approval of dostarlimab in the EU and USA marks a significant milestone in cancer treatment, highlighting its potential efficacy in targeting specific cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. Markham, A.[2021]

Dostarlimab (JEMPERLI) is a PD-1 monoclonal antibody that has received rapid FDA approval for treating adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, showing promising tumor response rates.

A clinical trial (NCT04165772) reported a remarkable 100% remission rate for rectal cancer patients treated with Dostarlimab, highlighting the potential of matching tumor genetics with targeted therapies, and the trial is ongoing for other cancer types like gastric, prostate, and pancreatic cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. Costa, B., Vale, N.[2022]

Dostarlimab, an investigational anti-PD-1 monoclonal antibody, shows promising clinical activity, especially in treating endometrial cancer, indicating its potential as a new treatment option.

This antibody is being explored both alone and in combination with other therapies for various cancers, including gynecological tumors, lung cancer, and melanoma, highlighting its broad applicability in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab for the treatment of endometrium cancer and other solid tumors. Rubio-Pérez, J., Hernández, R., Hernández, T., et al.[2021]

Dostarlimab-gxly (Jemperli) has received accelerated approval from the FDA for treating adults with mismatch repair deficient recurrent or advanced endometrial cancer and solid tumors, indicating its potential effectiveness in these specific cancer types.

This approval highlights the importance of targeted therapies in oncology, particularly for patients with specific genetic markers that may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. Aschenbrenner, DS.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2216334

Dostarlimab for Primary Advanced or Recurrent ... Dostarlimab plus carboplatin–paclitaxel significantly increased progression-free survival among patients with primary advanced or recurrent endometrial cancer.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36330672/

Dostarlimab for recurrent mismatch repair-deficient ... Dostarlimab is associated with greater survival compared with other treatments for women with recurrent dMMR endometrial cancer.

3. jemperli.com jemperli.com/endometrial-cancer/

Results for JEMPERLI | JEMPERLI (dostarlimab-gxly) JEMPERLI in combination with carboplatin and paclitaxel offers meaningful study results For people with newly-diagnosed advanced or returned endometrial cancer.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05201547

NCT05201547 | Endometrial Cancer Patientes MMR ... Phase 3, randomized, multicentre study to evaluate the efficacy and safety of dostarlimab versus carboplatin-paclitaxel in patients with MMR deficient relapse ...

5. jemperlihcp.com jemperlihcp.com/efficacy/garnet-trial/

GARNET Efficacy & Study Design - Jemperli Trial results from GARNET ... Of the 150 patients in the study with dMMR endometrial cancer who received JEMPERLI, 141 were included in the efficacy analysis.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1040842824001173

Dostarlimab: Review on success story and clinical trials Dostarlimab was developed by GlaxoSmithKline (GSK) for the treatment of various cancers including endometrial cancer, ovarian cancer, peritoneal ...

7. gsk.com gsk.com/en-gb/media/press-releases/us-fda-expands-jemperli-dostarlimab-plus-chemotherapy-approval-to-all-adult-patients-with-primary-advanced-or-recurrent-endometrial-cancer/

US FDA expands Jemperli (dostarlimab) plus ... Jemperli plus chemotherapy is the first and only immuno-oncology regimen to show significant and meaningful improvement in overall survival for adult patients.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02715284

NCT02715284 | Study of TSR-042, an Anti-programmed ... This is a multi-center, open-label, first-in-human Phase 1 study evaluating the anti-programmed death receptor 1 (anti-PD-1) antibody dostarlimab.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11252537/

Dostarlimab in the treatment of mismatch repair deficient ... Dostarlimab is an immunotherapy-based drug that has shown promising results in adult patients with recurrent or advanced dMMR EC.