A Phase I/II Trial Investigating LOAd703 in Combination With Atezolizumab in Malignant Melanoma

Inclusion Criteria

• Pathological confirmation of melanoma.
• A life expectancy of at least 3 months as per the investigator
• Valid for Swedish patients: Patients has locally advanced melanoma or metastatic melanoma, but not eligible for complete resection of melanoma Valid for US patients: Patients has locally advanced melanoma or metastatic melanoma.
• The patient has measurable disease (e.g., measurable tumor lesions must be present that can accurately be measured in at least one dimension with a minimum size of 10 mm by CT scan and MRI, 10 mm caliper measurement by clinical exam (when superficial), and/or 20 mm by chest X-ray).
• Patient has at least one injectable tumor lesion that has not been irradiated or has been irradiated but disease progression documented at the site subsequent to radiation therapy.
• The patient has received appropriate treatment with an anti-PD-1 or anti-PD-L1 antibody with or without an anti-CTLA4.
• Valid for Swedish patients: Patients whose advanced melanoma has a B-Raf mutation must have received appropriate therapy with tyrosine kinase inhibitor(s) and/or MEK inhibitor Valid for US patients: Patients whose advanced melanoma has a B-Raf mutation may have received appropriate therapy with tyrosine kinase inhibitor(s) and/or MEK inhibitor as assessed by the investigator.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Serum albumin ≥ 2.5 mg/dL.
• Absolute neutrophil count (ANC) ≥1.0 x 10e9/L.
• Platelet count ≥ 100 x 10e9/L.
• Prothrombin (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5 times ULN; and either partial thromboplastin time or activated partial thromboplastin time (PTT or aPTT) ≤ 1.5 times the ULN.
• Bilirubin 10 mg per day), lymphodepleting antibodies, or cytotoxic agents.
• Treatment with inhibitors of immune function, such as lymphotoxic monoclonal antibodies (e.g., alemtuzumab), or rapamycin/rapamycin analogs, or cytotoxic agents within 21 days of the first dose of LOAd703/atezolizumab.
• Therapeutic treatment with systemic antibiotics within 14 days of the first dose of LOAd703/atezolizumab.
• Treatment with biologic therapy within 21 days of the first dose of LOAd703/atezolizumab.
• Treatment with cytotoxic anticancer therapy within 14 days of the first dose of LOAd703/atezolizumab.
• Treatment with wide-field radiation within 14 days of the first dose of LOAd703/atezolizumab.
• Prior treatment with an adenovirus-based gene therapy.
• Use of any investigational agents within 21 days of the first dose of LOAd703/atezolizumab.
• The use of systemic immunostimulatory agents (including, but not limited to, interferons and IL2) are prohibited within 21 days or 5 half-lives (whichever is longer) of the first dose of LOAd703/atezolizumab.
• Failed resolution/improvement of AEs including those related to anti-PD-1/anti-PD-L1 to grade 0-1 and requirement for treatment with >10 mg/day prednisone (or equivalent) for at least two weeks prior to registration.
• History of CTCAE grade 4 immune-related AEs from monotherapy using an anti-PD-1/anti-PD-L1 antibody.
• History of CTCAE grade 4 AE that require steroid treatment (>10 mg/day prednisone or equivalent) for >12 weeks.
• Patients requiring warfarin are not eligible (low molecular weight heparin is permitted).
• Women who are pregnant (as confirmed by pregnancy test during screening in applicable patients), breastfeeding, or planning to become pregnant during the study period, or women of childbearing potential who are not using acceptable highly effective contraceptive methods. A woman is considered of childbearing potential if she is not surgically sterile or is less than 1 year since her last menstrual period. The following are acceptable as highly effective contraceptive methods: combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progesterone-only hormonal c