Malignant melanoma MedDRA version: 20.0 Level: HLT Classification code 10027156 Term: Skin melanomas (excl ocular) System Organ Class: 100000004858
Conditions
Interventions
Product Name: LOAd703
Product Code: LOAd703
Pharmaceutical Form: Suspension for injection
Trade Name: Tecentriq
Product Name: Tecentriq
Pharmaceutical Form: Concentrate for solution for infusion
Sponsors
Lokon Pharma AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Pathological confirmation of melanoma. 2. A life expectancy of at least 3 months as per investigator. 3. Patients has locally advanced melanoma or metastatic melanoma, but not eligible for complete resection of melanoma. 4. 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). 5. 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. 6. The patient has received appropriate treatment with an anti-PD-1 or anti-PD-L1 antibody with or without an anti-CTLA4. 7. Patients whose advanced melanoma has a B-Raf mutation must have received appropriate therapy with tyrosine kinase inhibitor(s) and/or MEK inhibitor as assessed by the investigator. 8. Age = 18 years. 9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 10. Serum albumin = 2.5 g/dL. 11. Absolute neutrophil count (ANC) = 1.0 x 10e9/L. 12. Platelet count = 100 x 10e9/L. 13. 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. 14. Bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1.Malignant melanoma that is uveal. 2.Subjects considered by the investigator to have a rapid progression of melanoma. 3. Patients must not have greater than 3 cerebral melanoma metastases, and/or clinically active cerebral melanoma metastases, and/or a requirement for corticosteroid therapy, and/or carcinomatous meningitis regardless of clinical stability. 4.Any concurrent treatment that would interfere with the effect mechanisms of atezolizumab and LOAd703, including, but not limited to, continuous high-dose corticosteroids (>10 mg per day), lymphodepleting antibodies, or cytotoxic agents. 5.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 first dose of LOAd703/atezolizumab. 6.Therapeutic treatment with systemic antibiotics within 14 days of first dose of LOAd703/atezolizumab. 7.Treatment with biologic therapy within 21 days of first dose of LOAd703/atezolizumab. 8. Treatment with cytotoxic anticancer therapy within 14 days of the first dose of LOAd703/atezolizumab. 9. Treatment with wide-field radiation within 14 days of the first dose of LOAd703/atezolizumab. 10. Prior treatment with an adenovirus-based gene therapy. 11. Use of any investigational agents within 21 days of the first dose of LOAd703/atezolizumab). 12. 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. 13. Failed resolution/improvement of AEs including those related to anti-PD-1/anti-PD-L1 antibody back to grade 0-1 and requirementfo treamtent with >10 mg/day prednisone (or equivalent) for at least two weeks prior to registration. 14. History of CTCAE grade 4 immune-related AEs from monotherapy using an anti-PD-1/anti-PD-L1 antibody 15. History of CTCAE grade 4 AE that require steroid treatment (12 weeks. 16. Patients requiring warfarin are not egible (low molecular weight heparin is permitted). 17.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 contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion and vasectomized partner or abstinence of heterosexual intercourse during the entire study period (depending on the preferred and usual life style of the subject). 18.Men who do not consent to the use of condoms during intercourse during study participation or has a partner of childbearing potential, who will not use any of the highly effective contraceptive methods exemplified in exclusion criteria no 17. 19.Known active hepatitis B or C infection, or HIV infection. 20.Patients with active, severe autoimmune disease or immune defici
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to determine the tolerability of LOAd703 administered by intratumoral injections in combination with intravenous atezolizumab. ;Secondary Objective: The secondary objectives are to determine the antitumor activity as well as the pharmacokinetics and biological mechanisms-of-action of LOAd703 in combination with atezolizumab. ;Primary end point(s): 1.The primary endpoint is safety, determined by the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE v5.0).;Timepoint(s) of evaluation of this end point: Vital signs before LOAd703 injection and then every 30 minutes for 2 hours, and at 3, 4, 5, 6, 8, 10, 14 hours post dose and then every 4 hours until discharge. If no immediate toxicities occurred after the first 2 treatments the patient will be observed for a minimum of 8 hours post injection at the 3rd and 4th injection, and for a minimum of 6 hours post injection. Prior to each LOAd703 and/or atezolizumab treatment (within -2 days), the Investigator must do a complete AE evaluation (including laboratory values and meeting the patient) and assess the toxicity screening to assure that the patient is able to receive further treatments | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Overall response rate evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST), v1.1. 2.Shedding determined as levels of LOAd703 in shedding samples at different time points post-treatment. 3.LOAd703 leakage to blood determined as levels of LOAd703 in blood at different time points post-treatment. 4.Anti-adenovirus immunity determined as anti-viral antibodies and T cells after combination therapy compared to baseline. 5.Pharmacokinetics of atezolizumab determined as the level of atezolizumab in blood at different time points post-treatment. 6.Immunity to atezolizumab determined as the level of anti-drug antibodies (ADA) targeting atezolizumab at different time points post-treatment compared to baseline. 7.Immune profile as determined by changes in immune cell populations and their activation markers in tumor tissue and blood after combination therapy compared to baseline. 8.Protein profile as determined by changes in protein profile in blood after combination therapy compared to baseline. ;Timepoint(s) of evaluation of this end point: 1.ORR every two months post-treatment initiation 2.LOAd703 in shedding samples pre-dose w 0, 1, 9, 18, 27, 33, 36, 45 and final FU. 24 hrs post- treatment w 0, 9, 18 and 27, and 7 d post-treatment w 1,19 and 34. 3.LOAd703 in blood pre-dose w 0, 1, 9, 18, 19, 27, 33, 34, 36, 45 and final FU. 24 hrs post- treatment w 0, 9, 18 27 and 33, and7 d post-treatment w 1,19 and 34. 4.Anti-adenovirus immunity w 0, 3, 6, 9, 21 and final FU 5.PK atezolizumab w 0, 3, 6, 9, 21 and final FU 6.ADA targeting atezolizumab w 0, 3, 6, 9, 21 and final FU 7.Changes in immune cell populations and their activation markers in tumor w 0, 9, 18, 27, 36, 45 and final FU 8.Changes in protein profile in blood w 0, 9, 18, 27, 36, 45 and final FU (immunology sampling); tumor biopsies w 0, 9 and 27 | — |
Countries
Sweden, United States
Contacts
Public ContactAnna Pauter
Lokon Pharma AB
Outcome results
None listed