Study of TSR-042 an Anti-programmed Cell Death-1 Receptor (PD-1) Monoclonal Antibody in Participants With Advanced Solid Tumors

  • STATUS
    Recruiting
  • End date
    Apr 4, 2024
  • participants needed
    740
  • sponsor
    Tesaro, Inc.
Updated on 15 May 2021
Investigator
US GSK Clinical Trials Call Center
Primary Contact
GSK Investigational Site (1.3 mi away) Contact
+187 other location
tyrosine
lymphoma
monoclonal antibodies
measurable disease
growth factor
endocrine therapy
treatment regimen
bilateral oophorectomy
x-rays
hormone therapy
fluoropyrimidine
erlotinib
EGFR
bevacizumab
pd-l1
cancer treatment
primary cancer
cancer chemotherapy
solid tumor
ovarian cancer
solid neoplasm
sarcoma
taxane
advanced malignant solid tumor
immunostimulants

Summary

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 (also known as TSR-042) n participants with advanced solid tumors who have limited available treatment options. The study will be conducted in 2 parts with Part 1 consisting of safety evaluation, pharmacokinetics (PK), and pharmacodynamics (PDy) of escalating doses of dostarlimab. Dose escalation will be based on ascending weight-based dose levels (DLs) of dostarlimab and will continue until the maximum tolerated dose (MTD) is reached or may be stopped at any dose level up to the highest dose of 20 milligrams per kilograms (mg/kg) based on emerging safety and PK/PDy data. Part 2 will be conducted in two subparts, Part 2A (fixed-dose safety evaluation cohorts) and Part 2B (expansion cohorts). Part 2A of the study will evaluate the safety and tolerability of dostarlimab at fixed doses of 500 mg administered every 3 weeks (Q3W) and 1000 mg administered every 6 weeks (Q6W). Part 2B of the study will examine the safety and clinical activity of dostarlimab in cohorts of participants with specific types of advanced solid tumors.

Details
Condition Cancer, Cancer/Tumors, Ewing's Family Tumors, Advanced or Metastatic Solid Tumors, Cancer (Pediatric), Neoplasms
Treatment TSR-042, dostarlimab
Clinical Study IdentifierNCT02715284
SponsorTesaro, Inc.
Last Modified on15 May 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Participant is at least 18 years of age
Participant has proven recurrent or advanced solid tumor and has disease progression after treatment with available anti cancer therapies, or is intolerant to treatment that meets the following requirements for the part of the study they will participate
in
a. Part 1: Any histologically or cytologically proven recurrent advanced solid tumor
b. Part 2A: : Any histologically or cytologically proven recurrent advanced solid tumor
c. Part 2B: Histologically of cytologically proven recurrent or advanced solid tumor with measurable lesion(s) per RECIST version 1.1 and meets one of the following disease types
The criteria below should be met for participant participating in
Cohort A1 (dMMR/MSI-H endometrial cancer) and
Cohort A2 (MMR-proficient/MSS endometrial cancer)
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
All endometrial cancer histologies are allowed except endometrial sarcoma (including carcinosarcoma)
Participants must submit 2 scans demonstrating increase in tumor measurement that meet criteria for PD on or after the latest systemic anti-cancer therapy based on RECIST 1.1 to Central Radiology prior to the first dose of dostarlimab
Presence of at least 1 measurable lesion on Baseline scan will be confirmed by central radiology review
Status of tumor MMR/MSI: Participants can be screened based on local MMR/MSI testing results using immunohistochemistry (IHC), polymerase chain reaction (PCR), or next generation sequencing (NGS) performed in a certified local laboratory, but participant eligibility needs to be determined by MMR IHC results. For participant with available local MMR IHC results for the respective cohort(s), tumor samples have to be submitted to a central IHC laboratory and its quality has to be checked and cleared prior to Cycle 1 Day 1 (C1D1). For participants without available local MMR IHC test results (participants with local PCR or NGS test results), central IHC results have to confirm eligibility prior to proceeding with other screening procedures. After the central IHC test is completed, remaining tumor tissue may be tested for further exploratory biomarkers or may be sent to a central NGS laboratory for further testing
Cohort E - Participants with NSCLC who progressed after at least 1 prior platinum-based systemic chemotherapy regimen for recurrent or advanced disease
Chemotherapy regimen in the adjuvant or neoadjuvant setting following surgery and/or radiation is acceptable if recurrent or advanced disease develops within 6 months from completion of therapy
Participants with a known epidermal growth factor receptor (EGFR) mutation must have received a chemotherapy regimen and an EGFR tyrosine-kinase inhibitor (TKI) (e.g., erlotinib, gefitinib, afatinib, or experimental)
Participants with a known anaplastic lymphoma kinase (ALK) translocation must have received a chemotherapy regimen and an ALK inhibitor (e.g., crizotinib, ceritinib or experimental)
Cohort F - Participants with recurrent or advanced dMMR/MSI-H solid tumors or POLE-mut solid tumors, except endometrial cancers, that have progressed following up to 2 prior lines of systemic therapy for recurrent or advanced (>=Stage IIIB) disease and who have no alternative treatment options. Prior treatment with hormone therapies alone given for recurrent or advanced disease is acceptable and does not count towards the number of anti-cancer therapies
dMMR/MSI-H colorectal cancer (CRC) participants must have progressed after or been intolerant to treatment with fluoropyrimidine, oxaliplatin, and irinotecan. Progression following up to 3 prior lines of therapy is allowed
Ovarian cancer participants with platinum-resistant disease (i.e., progression occurred <6 months on or after platinum doublet chemotherapy): receipt of up to 1 line of systemic therapy after becoming platinum-resistant is allowed
Participants must submit 2 scans demonstrating increase in tumor measurement that meet criteria for PD based on RECIST 1.1 to Central Radiology prior to the first dose of dostarlimab
Tumor MMR/MSI or POLE status: Participants can be screened based on local MMR/MSI testing results using immunohistochemistry (IHC), polymerase chain reaction (PCR), or next generation sequencing (NGS) performed in a certified local laboratory, but participant eligibility needs to be determined by MMR IHC results. For participants with available local MMR IHC results for the respective cohort(s), tumor samples have to be submitted to a central IHC laboratory and its quality has to be checked and cleared prior to C1D1. For participants without available local MMR IHC test results (participants with local PCR or NGS test results), central IHC results have to confirm eligibility prior to proceeding with other screening procedures. After the central IHC test is completed, remaining tumor tissue may be tested for further exploratory biomarkers or may be sent to a central NGS laboratory for further testing
Participants who are considered for the study based on POLE mutation must have the local results available showing tumor mutation(s) in the exonuclease domain of the POLE gene (amino acid residues 268-471) to begin screening. Participants must have the quality of submitted tumor samples checked and cleared by a central IHC laboratory prior to receiving study treatment
Cohort G: Participants must have recurrent high-grade serous, endometrioid, or clear cell ovarian, fallopian tube, or primary peritoneal cancer
Participants must have presence of at least 1 measurable lesion on Baseline scan that will be confirmed by central radiology review
Participants must be considered resistant to the last administered platinum therapy, that is, the time from the last administered platinum dose until the initial documented progression (as evidenced by radiographic progression per RECIST) must be less than 6 months
Participants must have completed at least 1 but no more than 3 prior lines of therapy for advanced or metastatic ovarian cancer. Neoadjuvant, adjuvant, and the combination of both will be considered as 1 line of therapy. Treatment with single-agent bevacizumab given as maintenance is not counted as a separate line of therapy. If a therapeutic regimen is modified or changed for a reason other than lack of response or PD (such as allergic reaction, toxicity, or drug availability), this is not counted as a separate line of therapy. The use of single-agent hormonal therapy given for reasons other than PD per RECIST v1.1 (i.e., hormonal therapy given for increasing Cancer antigen [CA]-125 levels) is not counted as a separate line of therapy
Participants must have been previously treated with platinum-based regimen, taxane agent(s), and bevacizumab (bevacizumab could be used as a single agent or in combination with another agent, in frontline therapy, as maintenance, or for treatment of recurrent disease)
Part 2B: Participants must have archival tumor tissue available that is formalin-fixed and paraffin-embedded
For participants who do not have archival tissue, a new biopsy must be performed to obtain a tissue sample prior to study treatment initiation. For participants without available archival tissue, the biopsy should be taken from the tumor lesions (either primary or metastatic) that have easy accessibility and low biopsy-associated risks and will exclude biopsies of the liver, brain, lung/mediastinum, pancreas, or endoscopic procedures extending beyond the esophagus, stomach or bowel
For Cohort G, participant must provide formalin fixed paraffin embedded (FFPE) tumor tissue block(s) with sufficient tumor content (as confirmed by the Sponsor's designated central laboratory) during screening to enable, for example, measures of homologous recombination pathway defects and PD-L1 status. The use of slides created from paraffin-embedded tissue as opposed to FFPE blocks must be approved by the Sponsor
Female participants must have a negative serum pregnancy test within 72 hours prior to the date of the first dose of study medication: unless they are of non-child bearing potential
Non child bearing potential is defined as: >= 45 years of age and has not had menses for > 1 year; Amenorrheic for < 2 years without a hysterectomy and oophorectomy and have a follicle- stimulating hormone (FSH) value in the postmenopausal range upon pre-study (screening) evaluation. Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound, magnetic resonance imaging (MRI) or computed tomography (CT) scan. Tubal ligation must be confirmed with medical records of the actual procedure
Female participants of childbearing potential must agree to use 1 highly effective form of contraception with their partner starting with the screening visit through 150 days after the last dose of study therapy
Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of <= 2 for Part 1 and <= 1 for Part 2
Participant has an adequate organ function

Exclusion Criteria

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
Participant has a known uncontrolled central nervous system (CNS) metastases and/or carcinomatous meningitis
Participant has a known additional malignancy that progressed or required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin, squamous cell cancer (SqCC) of the skin that has undergone potentially curative therapy, or in situ cervical cancer
Participant is considered a poor medical risk due to a serious, uncontrolled medical disorder, nonmalignant systemic disease or active infection requiring systemic therapy. Specific examples include, but are not limited to, active, non-infectious pneumonitis; uncontrolled ventricular arrhythmia; recent (within 90 days) myocardial infarction; uncontrolled major seizure disorder; unstable spinal cord compression; superior vena cava syndrome; or any psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study (including obtaining informed consent)
Participant is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the Screening Visit through 150 days after the last dose of study treatment
Participant has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
Participant has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
Participant has a known active hepatitis B (eg, hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (eg, hepatitis C virus ribonucleic acid (HCV RNA) (qualitative) is detected)
Participant has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease- modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Use of inhaled steroids, local injection of steroids, and steroid eye drops are allowed
Participant has as history of interstitial lung disease
Participant has not recovered (i.e., to <= Grade 1 or to Baseline) from radiation- and chemotherapy-induced AEs or received transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte-colony stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF] or recombinant erythropoietin) within 3 weeks prior to the first dose of study drug
Participant has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of study drug
Participant has received prior anti-cancer therapy (chemotherapy, targeted therapies, radiotherapy, or immunotherapy) within 21 days, or less than 5 times the half-life of the most recent therapy prior to study Day 1, whichever is shorter
Participant has not recovered adequately (<= Grade 1) from AEs and/or complications from any major surgery prior to starting therapy
Participant has received a live vaccine within 14 days of planned start of study therapy
Participant has a known hypersensitivity to dostarlimab components or excipients
For Cohort G, participants will not be eligible if they meet the following criteria
Participants who experienced disease progression within 3 months (as evidenced by radiographic progression per RECIST) of first-line platinum therapy
Participants with known deleterious or suspicious deleterious mutation in BRCA1 or BRCA2 genes (local testing permitted)
Participants has received prior therapy with a poly(adenosine diphosphate-ribose) polymerase (PARP)-1/PARP-2 inhibitor
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
Participant is immunocompromised. Participants with splenectomy are allowed
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