Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma

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Brief Title

Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma

Official Title

A Phase II Randomized, Open-label, Multi-center Study of the Safety and Efficacy of IMCgp100 Compared With Investigator Choice in HLA-A*0201 Positive Patients With Previously Untreated Advanced Uveal Melanoma

Brief Summary

      To evaluate the overall survival of HLA-A*0201 positive adult patients with previously
      untreated advanced UM receiving IMCgp100 compared to Investigator's Choice of dacarbazine,
      ipilimumab, or pembrolizumab.
    

Detailed Description

      This Phase II study is designed to evaluate the safety and efficacy of IMCgp100 compared with
      Investigator's Choice (dacarbazine, ipilimumab or pembrolizumab) in HLA-A*0201 positive adult
      patients with advanced UM treated in the first line setting with no prior systemic or
      liver-directed chemo-, radio- or immune-therapy administered in the advanced setting (prior
      surgical resection of liver metastases and adjuvant systemic therapy are acceptable).
      Comparison of the IMCgp100 efficacy results in this Phase II study will be made with the
      concurrently randomized arm (Investigator's Choice) with a primary endpoint of overall
      survival (OS) and secondary efficacy endpoints of progression-free survival (PFS), objective
      response rate (ORR), duration of response (DOR), and disease control rate (DCR).
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Overall survival defined as the time from patient inclusion to date of death due to any cause

Secondary Outcome

 Safety defined as the number of patients with treatment emergent adverse events, laboratory abnormalities, ECG changes, and/or physical examination findings

Condition

Uveal Melanoma

Intervention

IMCgp100

Study Arms / Comparison Groups

 IMCgp100
Description:  Biologic:IMCgp100 (Soluble gp 100-specific T cell receptor with anti - CD3 scFV: IMCgp100)

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

378

Start Date

October 16, 2017

Completion Date

March 2023

Primary Completion Date

October 2021

Eligibility Criteria

        Inclusion Criteria

          1. Male or female patients age ≥ 18 years of age at the time of informed consent

          2. Ability to provide and understand written informed consent prior to any study
             procedures

          3. Histologically or cytologically confirmed metastatic UM

          4. Must meet the following criteria related to prior treatment:

               -  No prior systemic therapy in the metastatic or advanced setting including
                  chemotherapy, immunotherapy, or targeted therapy

               -  No prior regional, liver-directed therapy including chemotherapy, radiotherapy,
                  or embolization

               -  Prior surgical resection of oligometastatic disease is allowed

               -  Prior neoadjuvant or adjuvant therapy is allowed provided administered in the
                  curative setting in patients with localized disease. Patients may not be
                  re-treated with an Investigator's Choice therapy that was administered as
                  adjuvant or neoadjuvant treatment. Additionally, patients who have received
                  nivolumab as prior adjuvant/neoadjuvant treatment should not receive
                  pembrolizumab as Investigator's Choice therapy.

          5. HLA A*0201 positive by central assay

          6. Life expectancy of > 3 months as estimated by the investigator

          7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at Screening

          8. Patients have measurable disease or non-measurable disease according to RECIST v1.1

          9. All other relevant medical conditions must be well-managed and stable, in the opinion
             of the investigator, for at least 28 days prior to first administration of study drug

        Exclusion Criteria

          1. Patient with any out-of-range laboratory values defined as:

               -  Serum creatinine > 1.5 × upper limit of normal (ULN) and/or creatinine clearance
                  (calculated using Cockcroft-Gault formula, or measured) < 50 mL/minute

               -  Total bilirubin > 1.5 × ULN, except for patients with Gilbert's syndrome who are
                  excluded if total bilirubin > 3.0 × ULN or direct bilirubin > 1.5 × ULN

               -  Alanine aminotransferase > 3 × ULN

               -  Aspartate aminotransferase > 3 × ULN

               -  Absolute neutrophil count < 1.0 × 109/L

               -  Absolute lymphocyte count < 0.5 × 109/L

               -  Platelet count < 75 × 109/L

               -  Hemoglobin < 8 g/dL

          2. History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs
             or monoclonal antibodies

          3. Clinically significant cardiac disease or impaired cardiac function, including any of
             the following:

               -  Clinically significant and/or uncontrolled heart disease such as congestive heart
                  failure (New York Heart Association grade ≥ 2), uncontrolled hypertension or
                  clinically significant arrhythmia currently requiring medical treatment

               -  QT interval corrected by Fridericia's formula (QTcF) > 470 msec on screening
                  electrocardiogram (ECG) or congenital long QT syndrome. NOTE: If the initial
                  automated QTcF is > 470 msec at screening, for the purpose of determining
                  eligibility, the mean QTcF, based on at least 3 ECGs obtained over a brief time
                  interval (ie, within 30 minutes), should be manually determined by a medically
                  qualified person.

               -  Acute myocardial infarction or unstable angina pectoris < 6 months prior to
                  Screening

          4. Presence of symptomatic or untreated central nervous system (CNS) metastases, or CNS
             metastases that require doses of corticosteroids within the prior 3 weeks to study Day
             1. Patients with brain metastases are eligible if lesions have been treated with
             localized therapy and there is no evidence of PD for at least 4 weeks by magnetic
             resonance imaging (MRI) prior to the first dose of study drug

          5. Active infection requiring systemic antibiotic therapy. Patients requiring systemic
             antibiotics for infection must have completed therapy at least 1 week prior to the
             first dose of study drug

          6. Known history of human immunodeficiency virus infection (HIV). Testing for HIV status
             is not necessary unless clinically indicated

          7. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional
             protocol. Testing for HBV or HCV status is not necessary unless clinically indicated
             or the patient has a history of HBV or HCV infection

          8. Malignant disease, other than that being treated in this study. Exceptions to this
             exclusion include the following: malignancies that were treated curatively and have
             not recurred within 2 years prior to study treatment; completely resected basal cell
             and squamous cell skin cancers; any malignancy considered to be indolent and that has
             never required therapy; and completely resected carcinoma in situ of any type

          9. Any medical condition that would, in the investigator's or Sponsor's judgment, prevent
             the patient's participation in the clinical study due to safety concerns, compliance
             with clinical study procedures or interpretation of study results

         10. Patients receiving systemic steroid therapy or any other systemic immunosuppressive
             medication at any dose level, as these may interfere with the mechanism of action of
             study treatment. Local steroid therapies (eg, otic, ophthalmic, intra-articular, or
             inhaled medications) are acceptable

         11. History of adrenal insufficiency

         12. History of interstitial lung disease

         13. History of pneumonitis that required corticosteroid treatment or current pneumonitis

         14. History of colitis or inflammatory bowel disease

         15. Major surgery within 2 weeks of the first dose of study drug (minimally invasive
             procedures such as bronchoscopy, tumor biopsy, insertion of a central venous access
             device, and insertion of a feeding tube are not considered major surgery and are not
             exclusionary)

         16. Radiotherapy within 2 weeks of the first dose of study drug, with the exception of
             palliative radiotherapy to a limited field, such as for the treatment of bone pain or
             a focally painful tumor mass

         17. Use of hematopoietic colony-stimulating growth factors (eg, G-CSF, GM-CSF, M-CSF) ≤ 2
             weeks prior to start of study drug. An erythroid-stimulating agent is allowed as long
             as it was initiated at least 2 weeks prior to the first dose of study treatment and
             the patient is not red blood cell transfusion dependent

         18. Pregnant, likely to become pregnant, or lactating women (where pregnancy is defined as
             the state of a female after conception and until the termination of gestation)

         19. Women of childbearing potential who are sexually active with a non-sterilized male
             partner, defined as all women physiologically capable of becoming pregnant, unless
             they are using highly effective contraception during study treatment (defined in
             Section 6.7), and must agree to continue using such precautions for 6 months after the
             final dose of investigational product; cessation of birth control after this point
             should be discussed with a responsible physician. Highly effective methods of
             contraception are described in Section 6.7

         20. Male patients must be surgically sterile or use double barrier contraception methods
             from enrollment through treatment and for 6 months following administration of the
             last dose of study drug

         21. Patients who are in an institution due to official or judicial order.

         22. Patients who are the investigator or any subinvestigator, research assistant,
             pharmacist, study coordinator, or other staff thereof, directly involved in the
             conduct of the study.

         23. Contraindication for treatment with Investigator's Choice alternatives (dacarbazine,
             ipilimumab and pembrolizumab) as per applicable labelling. Patient may have a
             contraindication to 1 or 2 of the choices if he/she is a candidate for dosing with at
             least 1 Investigator's Choice and meets all other study eligibility criteria.
      

Gender

All

Ages

18 Years - 99 Years

Accepts Healthy Volunteers

No

Contacts

Mohammed Dar, , 

Location Countries

Australia

Location Countries

Australia

Administrative Informations


NCT ID

NCT03070392

Organization ID

IMCgp100-202


Responsible Party

Sponsor

Study Sponsor

Immunocore Ltd


Study Sponsor

Mohammed Dar, Study Director, Immunocore Ltd


Verification Date

February 2021