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

NCT04123470 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: LOKON0032019-003300-12
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 3

Brief Summary

This study aims to evaluate safety and effect of combining an oncolytic adenovirus (delolimogene mupadenorepvec; LOAd703) with atezolizumab in patients with melanoma. LOAd703 will be administered intratumorally for up to 12 injections while atezolizumab will be administered intravenously for the duration of the active study visits (up to 57 weeks). The patients are then monitored for survival for maximum study participation of 48 months. The treatments will be given every 3 weeks. The patients will then be monitored for toxicity, PK, ADA, immune responses, virus shedding, tumor response by RECIST 1.1 and survival.

Conditions

Malignant Melanoma

Outcome Measures

Primary Outcomes (1)

• Tolerability Evaluated by NCI CTCAE v5.0

  The AE reporting period begins upon receiving the first LOAd703 and/or atezolizumab treatment and continues until final visit at week 57

  Up to 57 weeks post treatment initiation

Secondary Outcomes (6)

• Overall Response Rate

  Up to 57 weeks post treatment initiation

• Overall Survival

  From treatment initiation until last patient last visit, assessed up till 36 months

• Antibodies Against LOAd703

  Up to 57 weeks post treatment initiation

• Immune Cell Phenotype

  Up to 57 weeks post treatment initiation

• Virus Shedding

  Up to 57 weeks post treatment initiation

Study Arms (1)

Treatment

EXPERIMENTAL

Delolimogene mupadenorepvec plus atezolizumab

Genetic: delolimogene mupadenorepvec; Biological: atezolizumab

Interventions

delolimogene mupadenorepvec GENETIC

LOAd703 is an oncolytic adenovirus encoding TMZ-CD40L and 4-1BBL

Also known as: LOAd703

Treatment

atezolizumab BIOLOGICAL

Atezolizumab is an anti-PD-L1 antibody

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \< 1.5 times the institutional upper limit of normal (ULN).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 (≤ 5 if liver metastases are present) times the institutional ULN.

You may not qualify if:

• Malignant melanoma that is uveal.
• Subjects considered by the investigator to have rapid clinical progression due to melanoma
• Subjects 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.
• 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.
• 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.

Sponsors & Collaborators

• Lokon Pharma AB: lead
• Precision Oncology LLC: collaborator

Study Sites (3)

Cedars-Sinai Medical Center, The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

Baylor St Luke's Medical Center

Houston, Texas, 77030, United States

Location

Uppsala University Hospital

Uppsala, 75185, Sweden

Location

MeSH Terms

Conditions

Melanoma

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Angelica Loskog CEO
• Organization: Lokon Pharma

angelica.loskog@lokonpharma.com

+46 18-50 74 44

Study Officials

• Angelica Loskog, PhD

  Lokon Pharma AB

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants treated with LOAd703 at two dose levels (1x10e11 VP and 5x10e11VP) and fixed dose of atezolizumab

Study Record Dates

• First Submitted: October 9, 2019
• First Posted: October 11, 2019
• Study Start: January 28, 2020
• Primary Completion: July 30, 2023
• Study Completion: July 30, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); SE (1)