IO102-IO103 in Combination With Pembrolizumab Versus Pembrolizumab Alone in Advanced Melanoma (IOB-013/KN-D18)
- Conditions
- Patients with previously untreated, unresectable or metastatic (advanced) melanomaMedDRA version: 20.0Level: LLTClassification code 10027481Term: Metastatic melanomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-004594-32-CZ
- Lead Sponsor
- IO Biotech ApS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 380
1. Histologically or cytologically confirmed stage III (unresectable) or stage IV melanoma.
2. Patients are treatment naive, that is, no previous systemic anticancer therapy for unresectable or metastatic melanoma. For clarification, the following patients are eligible:
a. Patients with BRAFV600 mutation-positive melanoma are eligible if treatment naive and without rapidly progressive disease as per investigators assessment. Documented BRAFV600 mutation status must be available from all patients prior to trial entry.
b. Patients who have received previous adjuvant and/or neoadjuvant therapy with targeted therapy or immune therapy are eligible if administered the last dose at least 6 months before inclusion in this trial (randomization), and if relapse did not occur during active treatment or within 6 months of treatment discontinuation.
3. ECOG performance status score 0 or 1 assessed within 10 days before randomization
4. Life expectancy of >24 weeks per investigator assessment.
5. At least 1 measurable lesion according to RECIST v1.1 and confirmed by IRC.
6. Provision of archival (max 3 months), or newly acquired biopsy tissue not previously irradiated, and blood at screening for biomarker assessments. FFPE tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
Note:
• Use of archival tissue >3 months old, may be considered after communication with and agreement by the Sponsor.
• If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut (details pertaining to tumor tissue submission can be found in the Lab Manual).
7. Adequate organ function as defined by:
a. Haematology:
i. Absolute neutrophil count =1500/µL or =1.5 × 10^9/L
ii. Platelets =100,000/µL or =100 × 10^9/L
iii. Hemoglobin =9.0 g/dL or =5.6 mmol/L
b. Renal:
i. Creatinine =1.5 × upper limit of normal (ULN), or
ii. Measured or calculated creatinine clearance (CrCl) =60 mL/min for patients with creatinine levels > 1.5 × institutional ULN; Glomerular filtration rate can also be used in place of creatinine or CrCl
c. Hepatic:
i. Total bilirubin =1.5 × ULN or direct bilirubin = ULN for patients with total bilirubin levels between 1.5 × ULN and =3 × ULN
ii. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 × ULN (=5 × ULN for patients with liver metastases)
iii. Alkaline phosphatase =2.5 × ULN
d. Endocrine:
i. Thyroid stimulating hormone (TSH) within normal limits, or
ii. Total triiodothyronine (T3) is within normal limits, or
iii. Free T3 and free thyroxine (T4) are within the normal limits
e. Coagulation:
i. International randomized ratio, prothrombin time (PT) or activated PT time (aPTT) =1.5 × ULN unless patient is receiving anticoagulant therapy if PT or aPTT is within therapeutic range of intended use of anticoagulants
8. Has recovered from major surgery or radiation therapy–(> 30 Gray [Gy]) induced AEs.
9. AEs from previous anticancer therapies or interventions have resolved to at least Grade 1 or
baseline value from screening (except for alopecia). Patients with Grade be eligible. Patients with endocrine-related AEs Grade replacement may be eligible.
10. Patients are able and willing to provide written informed consent for the trial in accordance with ICH-GCP and local legislation before admission to the trial.
11. Aged =18 years on day of signing informed c
1. Uveal/ocular, acral or mucosal melanoma
2. Patients with known or suspected CNS metastases or with the CNS as the only site of active disease are excluded with the following exception:
• Patients with controlled (stable) brain metastases will be allowed to enroll
3. Patient has received previous radiotherapy within 2 weeks of start of trial treatment (visit 2). A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease.
4. Patients with BRAFV600-positive disease who are experiencing rapidly progressing disease and/or have received standard first-line therapy with BRAF and/or MEK inhibitor for unresectable or metastatic disease.
5. Active known or suspected autoimmune disease that required systemic treatment in the past 2 years.
6. Presence of other primary malignancies, with the exception of nonmelanoma skin cancer, carcinoma in situ or stage I nonulcerative melanoma, in situ cervical cancer, in situ breast cancer, and prostate cancer for patients who are receiving androgen deprivation therapy only.
7. Active infection requiring systemic therapy
8. History of active tuberculosis
9. Active noninfectious pneumonitis/interstitial lung disease or a history of noninfectious pneumonitis/interstitial lung disease which required systemic steroids
10. History of HIV infection. HIV testing is not required unless mandated by local health authorities.
For Czech Republic only: Note: HIV testing at Screening is required in the Czech Republic as mandated per local health authority.
11. Concurrent active hepatits B virus and /or concurrent Hepatitis C Virus infection.
For Czech Republic only: Note: Hepatitis B and C testing at Screening is required in the Czech Republic as mandated per local health authority..
12. Received a live or live-attenuated vaccine within 30 days before the first dose of trial treatment. Patients are also prohibited from receiving live or attenuated vaccine(s) throughout the duration of protocol therapy and/or within 90 days of the last dose of protocol therapy. Administration of killed vaccines, mRNA based (e.g., covid-19) and vector based vaccines are allowed.
13. Patient suffering from symptoms related to COVID-19 infection, who does not have immunity from vaccination or previous infection, and who cannot provide a negative PCR COVID-19 test from the last 72 hours.
14. Known or suspected hypersensitivity to components of IMP or PD-1 inhibitor.
15. Known adrenal insufficiency function (that is, basal cortisol level <140 nmol/L or < 5 µg/dL
16. Received any of the following medications or procedures:
a. Within 2 weeks before time of treatment initiation:
i. Systemic or topical corticosteroids at immunosuppressive doses >10 mg/day of hydrocortisone or >5 mg/day of prednisone equivalent. Inhaled or topical steroids and adrenal replacement steroid doses >5 mg/day prednisone equivalent are permitted in the absence of active autoimmune disease.
ii. Palliative radiation or gamma knife radiosurgery
iii. Treatment with complementary medications (e.g., herbal supplements or traditional Chinese medicines) to treat the disease being studied. Such medications are permitted if they are used as supportive care.
b. Within 4 weeks before time of treatment initiation:
i. Allergen hyposensitization therapy
ii. Growth factors
iii. Major surgery or the patient has not recovered from surgery at the time of treatment
initiation
17. In the opinion of the investigator, the patient is
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method