Safety and Efficacy of IMCgp100 Versus Investigator Choice in Advanced Uveal Melanoma
Condition: Uveal Melanoma
MeSH terms: Melanoma; Uveal Neoplasms
Intervention: IMCgp100; Dacarbazine; Ipilimumab; Pembrolizumab
Intervention description: IMCgp100 is to be administered at 20 mcg cycle 1 day1, then 30 mcg cycle 1 day 8, then 68 mcg cycle 1 day 15 and weekly thereafter by IV infusion over 15 minutes until confirmed disease progression or unacceptable toxicity; Dacarbazine is to be administered at 1,000 mg/m2 of body surface area IV infusion every 3 weeks until disease progression or unacceptable toxicity; Ipilimumab is to be administered at 3 mg/kg IV infusion over 90 minutes every 3 weeks for a total of 4 treatments; Pembrolizumab is to be administered at 2 mg/kg IV infusion up to a maximum of 200 mg administered Intravenously over 30 minutes every 3 weeks or 200 mg fixed dose administered intravenously every 3 weeks where approved locally until confirmed disease progression or unacceptable toxicity
Intervention MeSH terms: Pembrolizumab; Ipilimumab; Dacarbazine; Imidazole
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 378.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Melanoma; Uveal Cancer; IMCgp100; Immunotherapy; Tebentafusp; Ocular Melanoma; Eye Melanoma; Uveal Melanoma; Gp100; TCR; Dacarbazine; Ipilimumab; Pembrolizumab; Bispecific T cell receptor fusion protein; ImmTAC; Immune mobilizing monoclonal T cell receptor against cancer; Kimmtrak

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.
    

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. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at Screening

          7. Patients have measurable disease or non-measurable disease according to RECIST v1.1

          8. 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. Out-of-range laboratory values

          2. History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs
             or monoclonal antibodies

          3. Clinically significant cardiac disease or impaired cardiac function,

          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.