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    Summary
    EudraCT Number:2022-003289-18
    Sponsor's Protocol Code Number:219369
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Trial now transitioned
    Date on which this record was first entered in the EudraCT database:2022-12-21
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2022-003289-18
    A.3Full title of the trial
    A Phase 2, Single-Arm, Open-Label Study with Dostarlimab Monotherapy in Participants with Untreated Stage II/III dMMR/MSI-H Locally Advanced Rectal Cancer
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase 2 Study of Dostarlimab in Untreated dMMR/MSI-H Locally Advanced Rectal Cancer
    A.3.2Name or abbreviated title of the trial where available
    Phase 2 Study of Dostarlimab in Untreated dMMR/MSI-H Locally Advanced Rectal Cancer
    A.4.1Sponsor's protocol code number219369
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorGlaxoSmithKline Research & Development Limited
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportGlaxoSmithKline Research & Development Ltd
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGlaxoSmithKline Research & Development Ltd
    B.5.2Functional name of contact pointGSK Clinical Support Help Desk
    B.5.3 Address:
    B.5.3.1Street Address980 Great West Road
    B.5.3.2Town/ cityBrentford, Middlesex
    B.5.3.3Post codeTW8 9GS
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+44 800 783 9733
    B.5.6E-mailGSKClinicalSupportHD@gsk.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Jemperli
    D.2.1.1.2Name of the Marketing Authorisation holderGlaxoSmithKline (Ireland) Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDostarlimab
    D.3.2Product code TSR-042, GSK4057190A
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDostarlimab
    D.3.9.1CAS number 2022215-59-2
    D.3.9.2Current sponsor codeGSK4057190A
    D.3.9.3Other descriptive nameDostarlimab (50 mg/mL) Solution for Intravenous Infusion
    D.3.9.4EV Substance CodeSUB195307
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Untreated Stage II/III dMMR/MSI-H locally advanced rectal cancer
    E.1.1.1Medical condition in easily understood language
    Rectal Cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10038049
    E.1.2Term Rectal cancer stage II
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level PT
    E.1.2Classification code 10038050
    E.1.2Term Rectal cancer stage III
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    - To estimate the efficacy of dostarlimab in participants with Stage II/III (locally advanced) dMMR/MSI-H rectal cancer that has not been previously treated
    E.2.2Secondary objectives of the trial
    - To further estimate the efficacy of dostarlimab in participants with Stage II/III (locally advanced) dMMR/MSI-H rectal cancer that has not been previously treated
    - To assess the safety and tolerability of dostarlimab in participants with Stage II/III (locally advanced), dMMR/MSI-H rectal cancer that has not been previously treated
    - To describe the PK of dostarlimab in participants with Stage II/III (locally advanced), dMMR/MSI-H rectal cancer that has not been previously treated
    - To determine the immunogenicity of dostarlimab in participants with Stage II/III (locally advanced), dMMR/MSI-H rectal cancer that has not been previously treated
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Inclusion criteria (Prescreening Period)
    - A Prescreening Period will only be available at sites/countries where local dMMR/MSI-H testing is not available. The Prescreening Period is not required for participants whose dMMR/MSI-H status has been previously determined. Prior to Screening, participants without must meet the Prescreening criteria below.
    *Age
    Is at least 18 years of age at the time of signing the ICF.
    *Type of participant and disease characteristics
    1. Has histologically confirmed Stage II to III (T3-T4, N0, or T any, N+), locally advanced rectal cancer.
    2. Has radiologically and endoscopically evaluable disease.

    Inclusion criteria (Screening Period)
    Participants are eligible to be included in the study only if all the following criteria apply:
    *Age
    1. Is at least 18 years of age at the time of signing the ICF.
    * Type of participant and disease characteristics
    2. Has histologically confirmed Stage II to III (T3-T4, N0, or T any, N+), locally advanced rectal cancer.
    3. Has radiologically and endoscopically evaluable disease.
    4. Has a tumor demonstrating the presence of either:
    a. dMMR status; MMR status must be assessed by IHC for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of 1 or more proteins indicates dMMR; MMR status may be determined either locally or by the
    central reference laboratory; or b. MSI-H phenotype as determined by polymerase chain reaction or by tissue next-generation sequencing; MSI-H may be determined either locally or by the central reference laboratory.
    NOTE: Participants who are known to have Lynch syndrome and have been found to carry a specific germline mutation in an MMR gene (MLH1, MSH2, MSH6, PMS2) are eligible to participate.
    5. Has an archival FFPE tissue sample that must be available and submitted to the central reference laboratory for testing at Screening. If no archival tissue is available, a fresh baseline biopsy will be required.
    *Sex and contraceptive/barrier requirements
    Is willing to use adequate contraception.
    • Contraceptive use by female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
    Female participants:
    • A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies:
    • Is a WONCBP as defined in Appendix 4.
    OR
    • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), preferably with low user dependency, as described in Appendix 4, during the Intervention Period and for at least 120 days after the
    last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.
    • A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention.
    • If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
    • Additional requirements for pregnancy testing during and after study intervention as defined in Appendix 4.
    • The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.

    *Informed consent
    7. Is capable of giving signed informed consent as described in the protocol, including compliance with the requirements and restrictions listed in the ICF and in this
    protocol.

    * Performance status and organ function
    8. Has an ECOG performance status of 0 or 1.
    9. Has adequate organ function, as defined in Table 8. (NOTE: A complete blood count test should be obtained without transfusion or receipt of colony-stimulating factors within 2 weeks of obtaining the sample.)

    For a full list of Exclusion criteria please refer to the Study Protocol Section 5.1 Inclusion Criteria pp58-61
    E.4Principal exclusion criteria
    Participants are excluded from the study if any of the following criteria
    * Medical conditions
    1. Has distant metastatic disease.
    2. Has received prior radiation therapy, systemic therapy, or surgery for management of rectal cancer. Note: Endoscopy guided biopsy is not considered surgery.
    3. Has a tumor that, in the investigator’s judgment, is causing symptomatic bowel obstruction or otherwise requires urgent/emergent local intervention.
    4. Has a known additional malignancy that progressed or required active treatment within the past 2 years. Exceptions include adequately treated superficial skin cancers, superficial bladder cancers, and other in situ cancers.
    5. Is immunocompromised in the opinion of the investigator.
    6. 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)
    is not considered a form of systemic treatment.
    7. Is unable to undergo MRI.
    8. Has experienced any of the following with prior immunotherapy: any irAE of Grade ≥3, immune-related severe neurologic events of any grade (e.g., myasthenic syndrome/myasthenia gravis, encephalitis, Guillain-Barré Syndrome, or transverse myelitis), exfoliative dermatitis of any grade (Stevens-Johnson Syndrome, toxic epidermal necrolysis, or DRESS syndrome), or myocarditis of any grade. Non-clinically significant laboratory abnormalities are not exclusionary.

    * Prior/concomitant therapy
    9. Is receiving any other anticancer or experimental therapy. No other experimental therapies (including but not limited to chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene therapy, vaccine therapy, or other experimental drugs) of any kind are permitted while the participant is receiving study intervention.
    10. Is receiving immunosuppressive medication.
    11. Has received systemic corticosteroids (>10 mg daily prednisone or equivalent) within 7 days of first dose of study intervention. Use of inhaled steroids, local injection of steroids, topical steroids, and steroidal eye drops are allowed.
    12. Has received any live vaccine within 30 days prior to enrollment. Vaccination against COVID-19 using vaccines that are authorized via the appropriate regulatory mechanisms (e.g., Emergency Use Authorization, Conditional Marketing Authorization, or Marketing Authorization Application) are not exclusionary. Note: mRNA and adenoviral-based COVID-19 vaccines are considered non-live. If a COVID-19 vaccine is administered at any time, the date of COVID-19 vaccination must be entered in the eCRF.
    13. Is considered, in investigator’s opinion, a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active infection requiring systemic therapy. Specific examples include but are not limited to: 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).

    *Diagnostic assessments and other criteria
    14. Has documented presence of HBsAg at Screening or within 3 months prior to first dose of study intervention.
    15. Has a positive HCV antibody test result at Screening or within 3 months prior to first dose of study intervention. NOTE: Participants with a positive HCV antibody test result due to prior resolved disease can be enrolled if a confirmatory negative HCV RNA test is obtained.
    16. Has a positive HCV RNA test result at Screening or within 3 months prior to the first dose of study intervention. NOTE: The HCV RNA test is optional and participants with negative HCV antibody test are not required to undergo HCV RNA testing as well.

    For a full list of Exclusion criteria please refer to the Study Protocol Section 5.2 Inclusion Criteria pp61-63
    E.5 End points
    E.5.1Primary end point(s)
    - cCR12 as assessed by ICR, defined as maintenance of cCR for 12 months. The 12-month period starts from the first disease assessment after last dose of study intervention that demonstrates cCR by ICR.
    E.5.1.1Timepoint(s) of evaluation of this end point
    - cCR12 as assessed by ICR, defined as maintenance of cCR for 12 months. The 12-month period starts from the first disease assessment after last dose of study intervention that demonstrates cCR by ICR.
    E.5.2Secondary end point(s)
    - cCR36 as assessed by ICR, defined as maintenance of cCR for 36 months. The 36-month period starts from the first disease assessment after last dose of study intervention that demonstrates cCR by ICR.

    - EFS3 as assessed by investigator assessment, defined as remaining alive and free of 1) disease progression precluding surgery, 2) local recurrence, and 3) distant recurrence, as assessed by investigator at 3 years from the first dose of study
    intervention.

    EFS by investigator assessment defined as time from the date of first dose of study intervention to any of the following events:
    1) progression of disease that precludes surgery, 2) local recurrence, 3) distant recurrence (all as assessed by the investigator), or 4) death due to any cause
    • cCR12 by investigator assessment
    • cCR36 by investigator assessment
    • ORR by ICR, defined as achieving a PR, nCR, or cCR at PIDA or at least 4 weeks but no longer than 8 weeks after PIDA for participants with nCR or iCR (PIDA 2)
    • ORR at PIDA by investigator assessment
    • TME at 3 years, defined as undergoing TME, either as primary management or for local recurrence
    • DSS, Disease-Specific Survival, defined as time from the date of first dose of study intervention to death due to disease under study
    • DSS5, defined as not dying due to disease under study at 5 years from the first dose of study intervention
    • OS, defined as time from first dose of study intervention to death from any cause
    • OS5, defined as being alive at 5 years from first dose of study intervention

    - Frequency and severity of AEs, SAEs, irAEs, and AEs leading to death or discontinuation of study intervention
    - Serum concentrations and PK parameters (C-EOI and Ctrough) for dostarlimab
    - Incidence of ADA against dostarlimab
    E.5.2.1Timepoint(s) of evaluation of this end point
    - cCR36 as assessed by ICR, defined as maintenance of cCR for 36 months. The 36-month period starts from the first disease assessment after last dose of study intervention that demonstrates cCR by ICR.
    - EFS3 as assessed by investigator assessment, defined as remaining alive and free of 1) disease progression precluding surgery, 2) local recurrence, and 3) distant recurrence, as assessed by investigator at 3 years from the first dose of study
    intervention.
    -ORR by ICR, defined as achieving a PR, nCR, or cCR at PIDA or at least 4 weeks but no longer than 8 weeks after PIDA for participants with nCR or iCR (PIDA 2)
    -TME at 3 years, defined as undergoing TME, either as primary management or for local recurrence
    Please refer Table 6 in Protocol Page No. 51
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned21
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA24
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    Japan
    Korea, Republic of
    United States
    France
    Netherlands
    Spain
    Germany
    Italy
    United Kingdom
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days17
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days18
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 0
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 0
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 61
    F.4.2.2In the whole clinical trial 100
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2023-03-10
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-02-08
    P. End of Trial
    P.End of Trial StatusTrial now transitioned
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