What is the mechanism of action of this treatment?

Common treatments for tumors include immunotherapy, chemotherapy, and targeted therapies. Immunotherapy, such as anti-PD-1 antibodies like dostarlimab, works by blocking the PD-1 receptor on T-cells, thereby preventing cancer cells from evading the immune system and enhancing the body's ability to attack tumor cells. Chemotherapy targets and kills rapidly dividing cells, while targeted therapies inhibit specific genetic mutations that drive tumor growth. Understanding these mechanisms helps patients grasp how their treatments work, which can improve treatment adherence and outcomes.

What side effects are associated with this type of intervention?

Immune checkpoint inhibitors, such as dostarlimab, pembrolizumab, and nivolumab, commonly cause immune-related adverse events (irAEs) due to their mechanism of action, which enhances the immune system's activity against cancer cells. These side effects can affect various organ systems and include fatigue, rash, diarrhea, and endocrine disorders like hypothyroidism. More severe but less common irAEs include pneumonitis, hepatitis, colitis, and neurological complications. Management of these side effects often involves immunosuppressive treatments like corticosteroids.

What prior FDA approvals exist?

The FDA has approved several anti-PD-1 therapies for the treatment of various tumors. Pembrolizumab and nivolumab are notable examples, both approved for advanced non-small cell lung cancer (NSCLC) and melanoma, among other cancers. Pembrolizumab, for instance, has shown efficacy in NSCLC with different PD-L1 expression levels and is approved for use in both monotherapy and combination with chemotherapy. Nivolumab has been approved for previously treated advanced NSCLC and has demonstrated long-term benefits in several trials. These approvals highlight the effectiveness of anti-PD-1 therapies in managing advanced cancers, similar to the investigational use of dostarlimab in the treatment of advanced solid tumors.

What other types of research exist?

Promising alternatives to Dostarlimab for tumor patients include Pembrolizumab and Nivolumab, both of which are anti-PD-1 antibodies with extensive clinical trial data supporting their efficacy in various advanced solid tumors. Additionally, combination therapies such as Nivolumab plus Ipilimumab have shown effectiveness in multiple cancer types and may be considered as novel treatment options.

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Monoclonal Antibodies

Dostarlimab for Advanced Cancer (GARNET Trial)

Phase 1

Recruiting

Research Sponsored by Tesaro, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participants who have progressed on or after platinum doublet therapy

Participants have received no more than 2 lines of anti-cancer therapy for recurrent or advanced (>=Stage IIIB) disease. Prior treatment with hormone therapies is acceptable and does not count towards the number of anti-cancer therapies noted in the criterion above for this cohort.

Must not have

Participants has received prior therapy with a poly(adenosine diphosphate-ribose) polymerase (PARP)-1/PARP-2 inhibitor.

Participant has received prior therapy with an anti- programmed death receptor 1 (anti-PD-1), anti-PD-1- ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD- L2) agent.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840 and 1008 hours post dose q6w upto 2 years

Awards & highlights

No Placebo-Only Group

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Dostarlimab may cause immune-related side effects due to its action on the immune system, which could lead to inflammation in various organs. Other potential side effects include infusion reactions similar to allergic responses, fatigue, digestive issues like nausea or diarrhea, skin reactions, liver enzyme changes.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My condition worsened after platinum-based chemotherapy.

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

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My cancer has returned and is advanced.

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I have an EGFR mutation and have been treated with both chemotherapy and an EGFR inhibitor.

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I have 2 scans showing my cancer has grown after my last cancer treatment.

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I have ALK-positive cancer and have been treated with both chemotherapy and an ALK inhibitor.

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I have been treated with platinum, taxane, and bevacizumab for my cancer.

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My cancer returned within 6 months after my last platinum-based treatment.

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My condition worsened after platinum-based chemotherapy.

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My cancer has returned and is advanced.

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My tumor's MMR/MSI status was checked with a certified test.

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I have recurrent ovarian, fallopian tube, or peritoneal cancer with at least one measurable lesion.

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My cancer is endometrial, but not a sarcoma type.

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I have two scans showing my cancer has grown after my last cancer treatment.

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I am 18 years old or older.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been treated with a PARP inhibitor before.

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

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I have untreated brain metastases or cancer in the lining of my brain.

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I have been diagnosed with HIV.

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I still have significant side effects from a recent major surgery.

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I have active hepatitis B or C.

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I have a history of interstitial lung disease.

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I have an autoimmune disease treated within the last 2 years.

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I've had cancer treatment within the last 21 days or less than 5 half-lives of the treatment.

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I have a harmful BRCA1 or BRCA2 gene mutation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840 and 1008 hours post dose q6w upto 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840 and 1008 hours post dose q6w upto 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504, 672, 840 and 1008 hours post dose q6w upto 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Pharmaceutical Preparations

Part 1: Number of participants with abnormal clinical chemistry parameters

Part 1: Number of participants with abnormal electrocardiogram (ECG) parameters

+35 more

Secondary study objectives

Part 1: Area under the concentration-time curve at steady state (AUC,ss) of dostarlimab

Part 1: Area under the concentration-time curve from time 0 to infinity (AUC, 0-infinity) of dostarlimab

Part 1: Area under the concentration-time curve from time 0 to last (AUC,0-last) assessment of dostarlimab

+41 more

Side effects data

From 2022 Phase 2 trial • 18 Patients • NCT04409002

80%

Anemia

80%

Fatigue

73%

Abdominal pain

67%

CD4 lymphocytes decreased

67%

Alkaline phosphatase increased

67%

Nausea

60%

Anorexia

60%

Constipation

53%

Platelet count decreased

53%

Hyperglycemia

47%

Thromboembolic event

47%

Weight loss

47%

Anxiety

47%

Hypoalbuminemia

40%

Vomiting

40%

Peripheral motor neuropathy

40%

Blood bilirubin increased

40%

Dyspnea

40%

Hypertension

33%

Edema limbs

33%

Abdominal distension

33%

Aortic valve disease

33%

Back pain

33%

Diarrhea

33%

Fever

33%

Hypocalcemia

33%

Sinus tachycardia

27%

Depression

27%

White blood cell decreased

27%

Chills

27%

Ascites

27%

Hyponatremia

20%

Sore throat

20%

Urine discoloration

20%

Pain

20%

Paresthesia

20%

Delirium

20%

Cough

20%

Dizziness

20%

Lymphocyte count decreased

13%

Neutrophil count decreased

13%

Palpitations

13%

Insomnia

13%

Thrush

13%

Pain in extremity

13%

Confusion

13%

Dehydration

13%

Fall

13%

Cardiac troponin T increased

13%

Alanine aminotransferase increased

13%

Aspartate aminotransferase increased

13%

Bloating

13%

Dry mouth

13%

Dysphagia

13%

Dysuria

13%

Flatulence

13%

Gastroesophageal reflux disease

13%

Glucosuria

13%

Hiccups

13%

Hypercalcemia

13%

Hyperkalemia

13%

Hypokalemia

13%

Hypophosphatemia

13%

Hypothyroidism

13%

Localized edema

Urinary retention

Obesity

Urinary frequency

Oral hemorrhage

Oral pain

Skin infection

Stroke

Superficial thrombophlebitis

Hematuria

Hemorrhoidal hemorrhage

Erectile dysfunction

Generalized muscle weakness

Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify

Osteoporosis

Papulopustular rash

Tremor

Skin ulceration

Thyroid stimulating hormone increased

Encephalopathy

Endocarditis infective

Eye disorders - Other, specify

Pelvic pain

Prostatic obstruction

Pruritus

Rash acneiform

Rectal pain

Renal calculi

Reproductive system and breast disorders - Other, specify

Wheezing

Portal vein thrombosis

Vaginal dryness

Alopecia

Arthralgia

Arthritis

Bacteremia

Biliary tract infection

Blood lactate dehydrogenase increased

Buttock pain

Dry skin

Dysgeusia

Flank pain

Gastric anastomotic leak

Gastric ulcer

Gastritis

Gastrointestinal disorders - Other, specify

Gastrointestinal pain

Hyperlipidemia

Hypoglycemia

Lethargy

Memory impairment

Mucositis oral

Muscle cramp

Muscle weakness lower limb

Myocarditis

Restlessness

Scleral disorder

Sepsis

100%

80%

60%

40%

20%

Study treatment Arm

Niraparib+Dostarlimab + Radiation

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Dostarlimab

2019

Completed Phase 3

~2180

0 / 25Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for tumors include immunotherapy, chemotherapy, and targeted therapies. Immunotherapy, such as anti-PD-1 antibodies like dostarlimab, works by blocking the PD-1 receptor on T-cells, thereby preventing cancer cells from evading the immune system and enhancing the body's ability to attack tumor cells. Chemotherapy targets and kills rapidly dividing cells, while targeted therapies inhibit specific genetic mutations that drive tumor growth. Understanding these mechanisms helps patients grasp how their treatments work, which can improve treatment adherence and outcomes.