| Titre |
An Open-Label, Multicenter, Phase Ib Study To Evaluate Safety And Therapeutic Activity Of RO6874281, An Immunocytokine, Consisting Of Interleukin-2 Variant (Il-2v) Targeting Fibroblast Activation Protein-? (Fap), In Combination With Pembrolizumab (Anti-Pd-1), In Participants With Previously Untreated Advanced And/Or Metastatic Melanoma |
| Protocole ID |
BP41054 |
| ClinicalTrials.gov ID |
NCT03875079 |
| Type(s) de cancer |
Mélanome |
| Phase |
Phase I |
| Stade |
Maladie avancée ou métastatique |
| Type étude |
Traitement |
| Médicament |
RO6874281 avec Pembrolizumab |
| Institution |
CIUSSS DU CENTRE-OUEST-DE-L'ILE-DE-MONTREAL
 HOPITAL GENERAL JUIF SIR MORTIMER B.DAVIS
3755 rue de la Côte Ste. Catherine, Montréal, QC, H3T 1E2
|
| Ville |
Montréal |
| Investigateur(trice) principal(e) |
Dr Wilson Miller
|
| Coordonnateur(trice) |
Amanda Kasneci
514-340-8222 poste 26394
|
| Statut |
![]() Fermé |
| Critètes d'éligibilité |
- Participants with unresectable locally advanced (Stages IIIC and IIID) and metastatic (recurrent or de novo Stage IV) invasive cutaneous or mucosal melanoma that is measurable and who have not received prior treatment for advanced disease. Participants need to have known BRAF status. BRAF mutation-positive patients are eligible without prior treatment or after failure of BRAF directed inhibitor therapy
- Measurable disease, as defined by Response evaluation criteria in solid tumors version 1.1 (RECIST v1.1)
- Eastern Cooperative Oncology Group Performance Status 0 or 1 or Karnofsky Performance Score >= 70
- Life expectancy of >= 12 weeks
- Confirmed at least one tumor lesion with location accessible to safely biopsy per clinical judgment of the treating physician and the participant's consented willingness to undergo baseline tumor biopsies for Pharmacodynamic biomarker analysis
- Consent to provide an archival tumor tissue sample
- Adequate cardiovascular, hematological function, liver, renal function
- Adverse events related to any previous radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade <= 1, except alopecia and Grade 2 peripheral neuropathy
- Participants with unilateral pleural effusion are eligible
- Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, not a woman of childbearing potential or agrees to remain abstinent or use contraceptive methods that result in a failure rate of <= 1% per year during the treatment period and for at least 4 months after the last dose of study drug for RO6874281 and for at least 4 months after the last dose of pembrolizumab. Have a negative pregnancy test within the 7 days before the first study treatment administration.
- Male participants: Remain abstinent or use contraceptive measures such as a condom plus an additional contraceptive method that together result in a failure rate of <= 1% per year, with partners who are women of childbearing potential during the treatment period and for at least 2 months after the last dose of RO6874281. Refrain from donating sperm.
- Participants with Gilbert's syndrome will be eligible for the study. The diagnosis of Gilbert's syndrome is suspected in people who have persistent, slightly elevated levels of unconjugated bilirubin without any other apparent cause
|
| Critètes d'exclusion |
- Rapid disease progression or threat to vital organs or critical anatomical sites requiring urgent alternative medical intervention
- Symptomatic or untreated central nervous system (CNS) metastases
- History of treated asymptomatic Central Nervous System (CNS) metastases
- Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >= 2 weeks before enrollment
- Leptomeningeal disease
- An active second malignancy (exceptions are non-melanoma skin cancer, cervical carcinoma in situ, or prostate carcinoma that is in remission under androgen deprivation therapy for >= 2 years, or participants who have a history of malignancy and have been treated with curative intent and the participant is expected to be cured as per Investigator's assessment) - Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders, and known autoimmune diseases or other disease with ongoing fibrosis
- Episode of significant cardiovascular/cerebrovascular acute disease within 6 months before study treatment administration
- Active or uncontrolled infections, including latent tuberculosis
- Known human immunodeficiency virus (HIV) infection
- Active hepatitis B virus or hepatitis C virus infection
- Severe infection within 4 weeks before study treatment administration, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
- History of chronic liver disease or evidence of hepatic cirrhosis
- Dementia or altered mental status that would prohibit informed consent
- History of, active or suspicion of autoimmune disease (participants with autoimmune hypothyroidism and/or hypopituitarism may be eligible after consultation with Sponsor), idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography scan and radiation pneumonitis in the radiation field is permitted
- Bilateral pleural effusion confirmed by x ray
- Severe dyspnea at rest or requiring supplementary oxygen therapy
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that give reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
- Concurrent therapy with any other investigational drug
- Immunomodulating agents
- Treatment with systemic immunosuppressive medications including, but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti TNF agents within 2 weeks prior to Cycle 1 Day 1. Acute and/or low dose systemic immunosuppressive medications may be acceptable after consultation with the Sponsor
- Radiotherapy within the last 4 weeks before start of study treatment administration, with the exception of limited field palliative radiotherapy
- Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1
- Patients with previous treatment containing a checkpoint inhibitor (CPI) are not allowed in this study. Eligibility of participants who had received CPI as adjuvant treatment for previous localized disease need to be discussed and agreed upon with the Sponsor before screening
- Other Exclusions
- Major surgery or significant traumatic injury < 28 days before study treatment administration or anticipation of the need for major surgery during study treatment
- Known hypersensitivity to any of the components of the RO6874281 drug product or pembrolizumab drug product, including but not limited to hypersensitivity to Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies
- Participant eligibility for treatment with Pembrolizumab should be verified against the pembrolizumab labeling documents
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Groupe d'étude en oncologie du Québec