Clinical Trials /

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

NCT02715284

Description:

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.

Related Conditions:
  • Endometrial Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of TSR-042, an Anti-programmed Cell Death-1 Receptor (PD-1) Monoclonal Antibody, in Participants With Advanced Solid Tumors
  • Official Title: A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 213346
  • SECONDARY ID: 4010-01-001
  • NCT ID: NCT02715284

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
DostarlimabPart 1: Participants receiving dostarlimab

Purpose

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 evaluatation, 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.

Trial Arms

NameTypeDescriptionInterventions
Part 1: Participants receiving dostarlimabExperimentalPart 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
Part 2A: Participants receiving dostarlimabExperimentalIn 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.
  • Dostarlimab
Part 2B: Cohort A1 dMMR/MSI-HExperimentalPart 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.
  • Dostarlimab
Part 2B: Cohort A2 MMR-proficient/MSS endometrial cancerExperimentalPart 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.
  • Dostarlimab
Part 2B: Cohort E NSCLCExperimentalPart 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.
  • Dostarlimab
Part 2B:Cohort F non-endometrial dMMR/MSI-H & POLE-Mut cancersExperimentalParticipants with recurrent or advanced dMMR/MSI-H solid tumors or polymerase ɛ mutated (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. These participants will receive dostarlimab 500 mg for Q3W for the first 4 cycles followed by 1000 mg Q6W for all subsequent cycles.
  • Dostarlimab
Part 2B: Cohort G PROC without known BRCAExperimentalParticipants 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.
  • Dostarlimab

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Number of participants with treatment emergent AEs (TEAEs)
Time Frame:Up to 2 years
Safety Issue:
Description:An adverse event (AE) is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including clinically significant abnormal laboratory findings), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the product. TEAEs defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study treatment.

Secondary Outcome Measures

Measure:Part 2B: Cohort A1 ORR by independent blinded central review using RECIST version 1.1
Time Frame:Up to 2 years
Safety Issue:
Description:ORR is defined as the proportion of participants achieving CR or PR as assessed by investigator per RECIST version 1.1 will be evaluated.
Measure:Part 2B: Cohort F ORR by independent blinded central review using RECIST version 1.1
Time Frame:Up to 2 years
Safety Issue:
Description:ORR is defined as the proportion of participants achieving CR or PR as assessed by investigator per RECIST version 1.1 will be evaluated.
Measure:Part 2B: Cohort A1 Immune-related objective response rate (irORR) by irRECIST
Time Frame:Up to 2 years
Safety Issue:
Description:Immune related objective response rate will be evaluated.
Measure:Part 2B: Cohort A2 irORR by irRECIST
Time Frame:Up to 2 years
Safety Issue:
Description:Immune related objective response rate will be evaluated.
Measure:Part 2B: Cohort F irORR by irRECIST
Time Frame:Up to 2 years
Safety Issue:
Description:Immune related objective response rate will be evaluated.
Measure:Part 2B: Cohort G irORR by irRECIST
Time Frame:Up to 2 years
Safety Issue:
Description:Immune related objective response rate will be evaluated.
Measure:Part 2B: Cohort A1 Duration of response (DOR) based on independent blinded central review using RECIST version 1.1
Time Frame:Up to 2 years
Safety Issue:
Description:DOR is defined as the time from first documentation of CR or PR by RECIST version 1.1 until the time of first documentation of progressive disease (PD) evaluated using RECIST version 1.1 based on independent blinded central review, or death due to any cause.
Measure:Part 2B: Cohort F DOR based on independent blinded central review using RECIST version 1.1
Time Frame:Up to 2 years
Safety Issue:
Description:DOR is defined as the time from first documentation of CR or PR by RECIST version 1.1 until the time of first documentation of PD evaluated using RECIST version 1.1 based on independent blinded central review, or death due to any cause.
Measure:Part 2B: Cohort G DOR based on independent blinded central review using RECIST version 1.1
Time Frame:Up to 2 years
Safety Issue:
Description:DOR is defined as the time from first documentation of CR or PR by RECIST version 1.1 until the time of first documentation of PD evaluated using RECIST version 1.1 based on independent blinded central review, or death due to any cause.
Measure:Part 2B: Cohort A1 Disease control rate
Time Frame:Up to 2 years
Safety Issue:
Description:Disease control rate is the proportion of participants achieving CR, PR, or SD per RECIST v1.1 based on independent blinded central review.
Measure:Part 2B: Cohort A2 Disease control rate
Time Frame:Up to 2 years
Safety Issue:
Description:Disease control rate is the proportion of participants achieving CR, PR, or SD per RECIST v1.1 based on independent blinded central review.
Measure:Part 2B: Cohort F Disease control rate
Time Frame:Up to 2 years
Safety Issue:
Description:Disease control rate is the proportion of participants achieving CR, PR, or SD per RECIST v1.1 based on independent blinded central review.
Measure:Part 2B: Cohort G Disease control rate
Time Frame:Up to 2 years
Safety Issue:
Description:Disease control rate is the proportion of participants achieving CR, PR, or SD per RECIST v1.1 based on independent blinded central review.
Measure:Part 2B: Immune related disease control rate
Time Frame:Up to 2 years
Safety Issue:
Description:The proportion of participants achieving CR, PR, or SD per irRECIST based on Investigators' assessment.
Measure:Part 2B: Immune related duration of response
Time Frame:Up to 2 years
Safety Issue:
Description:The time from first documentation of CR or PR by irRECIST until the time of first documentation of PD (subsequently confirmed) per irRECIST based on Investigators' assessment.
Measure:Part 2B: Progression free survival
Time Frame:Up to 2 years
Safety Issue:
Description:The time from date of first dose to the earlier date of assessment of progression or death by any cause in the absence of progression based on: (1) the time of first documentation of PD per RECIST v1.1 (for Cohorts A1, A2, F, and G only); and (2) the time of first documentation of PD (subsequently confirmed) per irRECIST.
Measure:Part 2B: Overall survival
Time Frame:Up to 2 years
Safety Issue:
Description:The time from date of first dose of study treatment to the date of death by any cause.
Measure:Part 1: Area under the concentration-time curve from time 0 to last (AUC,0-last) assessment of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504 and 672 hours post dose
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 1: Area under the concentration-time curve from time 0 to infinity (AUC, 0-infinity) of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 1: Minimum concentration (Cmin) of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 1: Maximum concentration (Cmax) of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 1: Clearance (CL) of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 1: Volume of distribution (Vz) of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 1: Area under the concentration-time curve at steady state (AUC,ss) of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 1: Minimum concentration at steady state (Cmin,ss) of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose.
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 1: Maximum concentration at steady state (Cmax,ss) of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, 504,672 hours post dose
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2A : AUC,0-last assessment of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2A: AUC, 0-infinity of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2A: Cmin of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504,hours post dose Q3W upto 2 years
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected
Measure:Part 2A: Cmax of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504,hours post dose Q3W upto 2 years
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2A: CL of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504,hours post dose Q3W upto 2 years
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2A: Vz of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years.
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2A: AUC,ss of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2A: Cmin,ss of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2A: Cmax,ss of dostarlimab
Time Frame:Predose, 0.25, 0.5, 1.5, 3, 24, 48, 96, 168, 336, and 504 hours post dose Q3W upto 2 years
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2A : AUC,0-last assessment of dostarlimab
Time Frame: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
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2A: AUC, 0-infinity of dostarlimab
Time Frame: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
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2A: Cmin of dostarlimab
Time Frame: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
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2A: Cmax of dostarlimab
Time Frame: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
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2A: CL of dostarlimab
Time Frame: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
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2A: Vz of dostarlimab
Time Frame: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
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2A: AUC,ss of dostarlimab
Time Frame: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
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2A: Cmin,ss of dostarlimab
Time Frame: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
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2A: Cmax,ss of dostarlimab
Time Frame: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
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2B : AUC,0-last assessment of dostarlimab
Time Frame:Predose, 0.5 and 1.5 hours post dose
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2B: AUC, 0-infinity of dostarlimab
Time Frame:Predose, 0.5 and 1.5 hours post dose
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2B: Cmin of dostarlimab
Time Frame:Predose, 0.5 and 1.5 hours post dose
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2B: Cmax of dostarlimab
Time Frame:Predose, 0.5 and 1.5 hours post dose
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2B: CL of dostarlimab
Time Frame:Predose, 0.5 and 1.5 hours post dose
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2B: Vz of dostarlimab
Time Frame:Predose, 0.5 and 1.5 hours post dose
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2B: AUC,ss of dostarlimab
Time Frame:Predose, 0.5 and 1.5 hours post dose
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2B: Cmin,ss of dostarlimab
Time Frame:Predose, 0.5 and 1.5 hours post dose
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.
Measure:Part 2B: Cmax,ss of dostarlimab
Time Frame:Predose, 0.5 and 1.5 hours post dose
Safety Issue:
Description:Blood samples for determination of serum levels of dostarlimab will be collected.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Tesaro, Inc.

Trial Keywords

  • Metastatic solid tumors
  • Advanced solid tumors
  • anti-PD-1
  • TSR-042
  • Immunotherapy
  • PD-1
  • Endometrial
  • Non-small cell lung cancer, NSCLC
  • MSI-High
  • Dostarlimab
  • dMMR

Last Updated

March 25, 2020