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. ^{1 2 3 4 5}

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. ^{1 2 4 6 7}

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. ^{1 2 3 4 7}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

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.

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.

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 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.

Participant Groups

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.

Who Is Running the Clinical Trial?

Tesaro, Inc.

Lead Sponsor

Trials

57

Recruited

10,600+

Findings from Research

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-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]

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 (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, 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Dostarlimab: First Approval. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. United States 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. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Dostarlimab: A Review. [2022]

5. Spain pubmed.ncbi.nlm.nih.gov

Dostarlimab for the treatment of endometrium cancer and other solid tumors. [2021]

6. England pubmed.ncbi.nlm.nih.gov

A plain language summary of results from the GARNET study of dostarlimab in patients with endometrial cancer. [2023]

7. United States 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. [2023]