Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Iowa
Stay on your current meds
No Placebo Group
Prior Safety Data
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?This trial is testing the immunotherapy drug dostarlimab in patients with Stage II and III colon cancer. The goal is to see if the drug can shrink the tumors enough to avoid surgery. Dostarlimab helps the immune system attack the cancer cells.
Do I need to stop my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy or have an active autoimmune disease requiring treatment, you may not be eligible to participate.
What data supports the effectiveness of the drug dostarlimab for colon cancer?
Dostarlimab has shown promising results in treating mismatch repair-deficient rectal cancers, with a study reporting a 100% remission rate. This suggests potential effectiveness for similar conditions like colon cancer, especially if they share genetic characteristics.
12345Is dostarlimab safe for humans?
Dostarlimab has been approved for use in certain cancers, and studies have shown it to be generally well tolerated in humans, with clinical trials indicating it is safe for use in treating advanced cancers. It has been tested in both animal models and human trials, showing promising safety results.
12367Eligibility Criteria
This trial is for adults with Stage II or III colon cancer that hasn't spread, can be surgically removed, and has a specific abnormality called dMMR. Participants must have normal organ function tests, understand the study requirements, and agree to use contraception. Those with recent major surgery, live vaccines, other cancers within two years, uncontrolled illnesses, certain infections like HIV/HBV/HCV or active autoimmune diseases are excluded.Inclusion Criteria
My colon cancer biopsy has enough tissue for the required tests.
I am fully active and can carry on all my pre-disease activities without restriction.
My colon cancer is at Stage II or III and can be surgically removed in one piece.
I am 18 years old or older.
Exclusion Criteria
I do not have a tumor that is blocking any organs.
I have not had any other major cancers in the last two years.
I have not received a live vaccine in the last 30 days.
I do not have any serious illnesses or social situations that would stop me from following the study's requirements.
I do not have active bleeding from colon cancer.
I have a weak immune system or recently had treatment that lowers my immunity.
I have had interstitial lung disease in the past.
Participant Groups
The trial is testing Dostarlimab's effectiveness in shrinking colon cancer before surgery. Patients will receive up to six cycles of Dostarlimab over 18 weeks and their response will be monitored to see if they can avoid surgery.
1Treatment groups
Experimental Treatment
Group I: Neoadjuvant DostarlimabExperimental Treatment1 Intervention
Participants will receive Dostarlimab 500 mg IV every 3 weeks for 9 cycles followed by 1000 mg every 6 weeks for 12 cycles until 2 years
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:
University of Iowa Hospitals & ClinicsIowa City, IA
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Who is running the clinical trial?
University of IowaLead 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.
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.
Defying all odds in MMR-deficient rectal cancers. [2022]Neoadjuvant treatment with immunotherapy using dostarlimab leads to impressive clinical responses and omission of surgery in patients with mismatch repair (MMR)-deficient rectal cancers, according to a study published in the New England Journal of Medicine.
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).
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.
Preclinical characterization of dostarlimab, a therapeutic anti-PD-1 antibody with potent activity to enhance immune function in in vitro cellular assays and in vivo animal models. [2022]Inhibitors of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) have dramatically changed the treatment landscape for patients with cancer. Clinical activity of anti-PD-(L)1 antibodies has resulted in increased median overall survival and durable responses in patients across selected tumor types. To date, 6 PD-1 and PD-L1, here collectively referred to as PD-(L)1, pathway inhibitors are approved by the US Food and Drug Administration for clinical use. The availability of multiple anti-PD-(L)1 antibodies provides treatment and dosing regimen choice for patients with cancer. Here, we describe the nonclinical characterization of dostarlimab (TSR-042), a humanized anti-PD-1 antibody, which binds with high affinity to human PD-1 and effectively inhibits its interaction with its ligands, PD-L1 and PD-L2. Dostarlimab enhanced effector T-cell functions, including cytokine production, in vitro. Since dostarlimab does not bind mouse PD-1, its single-agent antitumor activity was evaluated using humanized mouse models. In this model system, dostarlimab demonstrated antitumor activity as assessed by tumor growth inhibition, which was associated with increased infiltration of immune cells. Single-dose and 4-week repeat-dose toxicology studies in cynomolgus monkeys indicated that dostarlimab was well tolerated. In a clinical setting, based on data from the GARNET trial, dostarlimab (Jemperli) was approved for the treatment of adult patients with mismatch repair-deficient recurrent or advanced endometrial cancer that had progressed on or following prior treatment with a platinum-containing regimen. Taken together, these data demonstrate that dostarlimab is a potent anti-PD-1 receptor antagonist, with properties that support its continued clinical investigation in patients with cancer.
A novel trial methodology to test interventions with very large effect sizes: the case of dostarlimab in mismatch repair-deficient, locally advanced rectal cancer. [2022]Dostarlimab (Jemperli, GlaxoSmithKline) is an anti-programmed death receptor-1 monoclonal antibody (anti-PD-1) recently tested in a non-randomized, phase II trial (NCT04165772) which included patients with mismatch repair-deficient, locally advanced rectal cancer. Among the first 12 patients treated with dostarlimab, 100% achieved a clinical complete response with no patients experiencing progression or recurrence to date. Most impressive, none required chemotherapy, radiotherapy or surgery the prevailing standard of care. In this paper, we discuss the impressive results of this trial and how they relate to cancer policy, as well as propose a novel trial methodology to assess dostarlimab.