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


Protocolnummer:

Ziekenhuizen:
Leids Universitair Medisch Centrum

Titel:

A Phase II Randomized, Open-label, Multi-center Study of the Safety and

Efficacy of IMCgp100 Compared with Investigator’s Choice in HLA-A*0201

Positive Patients with Previously Untreated Advanced Uveal Melanoma

Behandeling:

Stadium:
Oogmelanoom

Belangrijkste in/exclusiecriteria:

Inclusiecriteria

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 local, liver-directed therapy including chemotherapy,

radiotherapy, radiofrequency ablation (RFA), or embolization

• Prior surgical resection of oligometastatic liver 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

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 must have measurable disease according to RECIST v.1.1

criteria

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

Exclusiecriteria:

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

• Potassium, magnesium, corrected calcium or phosphate

abnormality of National Cancer Institute Common Terminology

Criteria for Adverse Events (NCI CTCAE) grade > 1

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

• QTcF > 470 msec on screening electrocardiogram (ECG) or

congenital long QT syndrome

• 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 progression 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,

GMCSF, 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 child-bearing potential who are sexually active with a nonsterilized

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

Contactpersoon:
Dr. E. Kapiteijn, LUMC

Alle melanoom trials