Solid tumors and lymphoma (lymph tissue cancer)
Conditions
Interventions
MIW815 (intra tumoral) - increasing dose. 2 schedules
A) day 1-8 and 15 in a 4-week cycle
B) day 1 in a 4-week cycle
PDR001: fixed dose every 4 weeks, administered intravenously in 100ml glucose
MIW815 (ADU-S100)
PDR001
Sponsors
Novartis
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Male and female *18 years of age. 2. Measurable disease as determined by RECIST v1.1 (for solid tumors) or Cheson 2014 criteria (for lymphoma). 3. At least two sites of disease amenable to biopsy, and willing to undergo new tumor biopsy at screening and during therapy. See protocol page 30-31 for details. 4. Dose escalation part: Advanced/metastatic solid tumors or lymphomas that have progressed despite standard therapy or where standard therapy is not tolerated, for whom no standard therapy exists or for whom standard therapy is not reasonably effective. 5. Dose expansion part: Melanoma patients with accessible cutaneous or subcutaneous lesions, who have relapsed or progressed after responding to a PD-1 inhibitor or who are refractory to PD-1 Inhibitors, HNSCC or patients with other accessible cutaneous or subcutaneous solid tumors and lymphomas, that have progressed despite standard therapy or are intolerant of standard therapy, for whom no standard therapy exists or for whom standard therapy is not reasonably effective. In addition, patients with injectable visceral lesions who have MSS CRC or other solid tumors with accessible visceral lesions, who have progressed despite standard therapy or are intolerant of standard therapy, for whom no standard therapy exists or for whom standard therapy is not reasonably effective. 6. ECOG performance status 0-1
Exclusion criteria
Exclusion criteria: 1. Patients who require immediate local palliative measures such as XRT or surgery. 2. Symptomatic or untreated leptomeningeal disease. 3. Symptomatic -CNS metastases, see protocol page 31 for details. 4. Laboratory abnormalities: - Creatinine > 1.5 x upper limit of normal (ULN) - Total bilirubin > 1.5 x ULN (except for Gilbert*s syndrome > 3.0 x ULN) - ALT and AST (liver) > 3 x ULN (except when livermetastasis > 5 x ULN_ - Absolute neutrophil count 1.5 x ULN and/or aPTT > 1.5 x ULN, except for patients in Group C: INR and aPTT must be normal - Hemoglobin (Hgb) grade 1 using CTCAE v4.03 5. Impaired cardiac function or clinically significant cardiac disease, see protocol page 42 for details. 6. Active, known or suspected autoimmune disease or a documented history of autoimmune disease, see protocol page 43 for details. 7. Active infection requiring systemic antibiotic therapy. 8. Cytotoxic or targeted antineoplastics within 14 days prior to the first dose of study treatment, see protocol page 43 for details. 9. Systemic chronic steroid therapy (* 10mg/day prednisone or equivalent) or any immunosuppressive therapy 7 days prior to start of study treatment. 10. Use of any live vaccines against infectious diseases within 4 weeks of initiation of study treatment. 11. Use of G-CSF and comparable, see protocol page 43/44 for details.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Iincidence and severity of (serious) adverse events, including changs in laboratory parameters, vital signs, ECGs, incidence of DLT during the 1st cycle. | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall response rate, progression free survival, duration of response, disease control rate, PK parameters. Antidrug antibodies. Tumor Infiltrating lymphocytes in (non-)injected lesions. | — |
Countries
The Netherlands
Outcome results
None listed