Dostarlimab for Advanced Cancer
(GARNET Trial)
Recruiting in Palo Alto (17 mi)
+110 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Tesaro, Inc.
Must not be taking: Immunosuppressants, Steroids
Disqualifiers: Uncontrolled CNS metastases, Active autoimmune, others
No Placebo Group
Breakthrough Therapy
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
This trial is testing dostarlimab, a medicine that helps the immune system fight cancer, in patients with advanced solid tumors who have limited treatment options. It works by blocking a protein that allows cancer cells to hide from the immune system. Dostarlimab has garnered extensive interest for its ability to activate the immune system to respond to cancer cells.
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.
What data supports the effectiveness of the drug Dostarlimab for advanced cancer?
Dostarlimab has shown promising results in treating certain types of advanced cancers, particularly endometrial cancer, where it has been approved for use in patients with specific genetic markers. In a clinical trial, it achieved a 100% remission rate for rectal cancer, indicating its potential effectiveness in matching treatment to the genetic drivers of tumors.12345
Is dostarlimab safe for humans?
Dostarlimab has been tested in clinical trials, such as the GARNET study, to evaluate its safety and side effects in treating certain types of cancer, including endometrial cancer. The FDA has granted accelerated approval for its use, indicating that it has been deemed safe enough for specific conditions, but ongoing studies are required to confirm its long-term safety.12467
How is the drug dostarlimab unique for treating advanced cancer?
Dostarlimab is unique because it is a monoclonal antibody that targets the PD-1 receptor, helping the immune system attack cancer cells, and it has shown promising results in treating cancers with specific genetic features, like mismatch repair deficiency, which are often resistant to other treatments.12347
Eligibility Criteria
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.
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Exclusion Criteria
I have been treated with a PARP inhibitor before.
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 drugs targeting the PD-1 or PD-L1/L2 pathways.
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Trial Timeline
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
Treatment Details
Interventions
- Dostarlimab (Monoclonal Antibodies)
Trial OverviewThe 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.
Participant Groups
7Treatment groups
Experimental Treatment
Group I: Part 2B:Cohort F non-endometrial dMMR/MSI-H & POLE-Mut cancersExperimental Treatment1 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 BRCAExperimental Treatment1 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 NSCLCExperimental Treatment1 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 cancerExperimental Treatment1 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 cancerExperimental Treatment1 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 dostarlimabExperimental Treatment1 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 dostarlimabExperimental Treatment1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
GSK Investigational SiteOklahoma City, OK
GSK Investigational SiteKansas City, MO
GSK Investigational SiteCharlotte, NC
GSK Investigational SiteSan Francisco, CA
More Trial Locations
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Who Is Running the Clinical Trial?
Tesaro, Inc.Lead Sponsor
References
Dostarlimab: First Approval. [2021]Dostarlimab (Jemperli™; GlaxoSmithKline) is a humanized monoclonal antibody programmed death-1 (PD-1) receptor antagonist being developed for the treatment of various cancers. Based on preliminary results from the GARNET trial dostarlimab has recently been approved in the EU and USA for the treatment of adult patients with mismatch repair deficient recurrent or advanced endometrial cancer. This article summarizes the milestones in the development of dostarlimab leading to these first approvals.
New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. [2023]The Food and Drug Administration (FDA) has granted accelerated approval to dostarlimab-gxly (Jemperli) for the treatment of adults with mismatch repair deficient recurrent or advanced endometrial cancer and solid tumors.
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. [2023]Dostarlimab is an anti-programmed cell death protein-1 antibody being evaluated in recurrent/advanced solid tumors, including non-small cell lung cancer (NSCLC), in the ongoing Phase I, multi-center, open-label, 2-part (dose escalation and cohort expansion) GARNET study (NCT02715284).
Dostarlimab: A Review. [2022]Dostarlimab (JEMPERLI) is a PD-1 monoclonal antibody for the treatment of adult patients, with mismatch repair deficient (dMMR), recurrent or advanced endometrial cancer that has progressed on or following prior therapy with a platinum-containing regimen. As determined by an FDA-approved test this indication was granted rapid approval based on the rate of tumor response and the duration of the response. Continued approval for this indication is conditioned on further confirmatory trials demonstrating and documenting clinical benefit. In June 2022, the clinical trial NCT04165772 reported a 100% remission rate for rectal cancer. This clinical trial brought proof that we can match a tumor and the genetics of what is driving it, with therapy. This clinical trial continues to enroll patient and is currently enrolling patients with gastric, prostate, and pancreatic cancers. Dostarlamib is being recommended for rectal cancer. The focus of this review is to summarize the existing knowledge regarding Dostarlimab and explore the possibilities of mono- and combination therapies.
Dostarlimab for the treatment of endometrium cancer and other solid tumors. [2021]The use of monoclonal antibodies directed against programmed cell death protein 1 (PD-1) and its ligand, programmed cell death 1 ligand 1 (PD-L1), widely extends to a large number of tumors such as melanoma, non-small cell lung, renal or lymphomas, among others. Some of them are already approved as first- or second-line treatment, as pembrolizumab, nivolumab or cemiplimab. Dostarlimab is an investigational humanized anti-PD-1 that is being developed both in monotherapy and as combination therapy, for gynecological tumors but also for lung cancer or melanoma. The preliminary results, particularly in endometrial cancer, show a high affinity against PD-1 with encouraging clinical activity. Here we summarize the development of this compound as well as the current preclinical and clinical data and potential future development.
A plain language summary of results from the GARNET study of dostarlimab in patients with endometrial cancer. [2023]Dostarlimab, also known by the brand name JEMPERLI, is a medicine that can be used to treat certain types of endometrial cancer. GARNET is an ongoing phase 1 clinical study that is testing the safety and side effects of dostarlimab and the best way to administer it to patients. The results presented in this summary are from a time point in the middle of the study.
Comparative analysis of PD-1 target engagement of dostarlimab and pembrolizumab in advanced solid tumors using ex vivo IL-2 stimulation data. [2023]Dostarlimab (JEMPERLI) is an anti-programmed cell death protein-1 (PD-1) monoclonal antibody (mAb) which is approved by the US Food and Drug Administration for patients with recurrent/advanced mismatch repair-deficient solid tumors, including endometrial cancer, following progression on prior treatment, with approval based on data from the phase I GARNET trial. To support dostarlimab dose regimen recommendations, we estimated and compared the potency of dostarlimab relative to anti-PD-1 mAb pembrolizumab using both data published from the KEYNOTE-001 trial of pembrolizumab and data from the GARNET trial. PD-1 target engagement was assessed ex vivo in blood samples via a super antigen staphylococcal enterotoxin B stimulation assay and interleukin-2 (IL-2) stimulation ratios calculated for dostarlimab. A non-linear mixed-effect sigmoid maximum effect inhibitory model was fitted to dostarlimab IL-2 stimulation ratios using extracted pembrolizumab data as informative priors. The estimated half-maximal effective concentration was 1.95 μg ml-1 (95% credibility interval: 0.21-5.87) for dostarlimab and 1.59 μg ml-1 (95% confidence interval: 0.42-6.12) for pembrolizumab. These findings suggest dostarlimab and pembrolizumab to be equipotent for peripheral PD-1 suppression based on analysis of ex vivo IL-2 stimulation ratios. Accounting for a three-fold dilution between serum and tumor, a target dostarlimab trough concentration of ~54 μg ml-1 would be needed for 90% suppression in the tumor. These data support the use of dostarlimab as a potent PD-1 suppressor and the recommended dostarlimab monotherapy dose regimen of 500 mg Q3W ×4 cycles followed by 1000 mg Q6W thereafter in recurrent/advanced solid tumors.