Clinical Trials /

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

NCT04123470

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase I/II Trial Investigating LOAd703 in Combination With Atezolizumab in Malignant Melanoma
  • Official Title: A Phase I/II Trial Investigating LOAd703 in Combination With Atezolizumab in Malignant Melanoma

Clinical Trial IDs

  • ORG STUDY ID: LOKON003
  • SECONDARY ID: 2019-003300-12
  • NCT ID: NCT04123470

Conditions

  • Malignant Melanoma

Interventions

DrugSynonymsArms
atezolizumabTreatment

Purpose

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 study visits (up to 57 weeks). 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.

Detailed Description

      This is a single arm, open-label, multicenter trial. This study aims to evaluate safety and
      effect of combining an oncolytic adenovirus (delolimogene mupadenorepvec; LOAd703) with
      atezolizumab in patients with melanoma. Patients will receive up to 12 LOAd703 intratumoral
      treatments in combination with intravenous infusions of atezolizumab. LOAd703 will be tested
      at two dose levels to determine the maximum tolerated dose (MTD) of LOAd703 evaluated in the
      study using a BOIN design. The LOAd703 dose can be divided for intratumoral injection into as
      many as 3 tumor lesions. Atezolizumab will be tested at a fixed dose. At least 25 response
      evaluable patients will be enrolled at the MTD for evaluation of their response using
      binominal testing. The maximum number of evaluable patients in the study is 35. The patients
      will then be monitored for toxicity, PK, ADA, immune responses, virus shedding, tumor
      response by RECIST 1.1 and survival.
    

Trial Arms

NameTypeDescriptionInterventions
TreatmentExperimentalDelolimogene mupadenorepvec plus atezolizumab
  • atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Pathological confirmation of melanoma.

          2. Patients not eligible for complete resection of advanced melanoma.

          3. 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).

          4. 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.

          5. The patient has received appropriate treatment with an anti-PD-1 or anti-PD-L1
             antibody with or without an anti-CTLA4.

          6. Patients whose advanced melanoma has a B-Raf mutation must have received appropriate
             therapy with tyrosine kinase inhibitor(s) and/or MEK inhibitor.

          7. Age > 18 years.

          8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

          9. Serum albumin ≥ 3.0 mg/dL.

         10. Absolute neutrophil count (ANC) > 1.0 x 10e9/L.

         11. Platelet count ≥ 100 x 10e9/L.

         12. 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.

         13. Bilirubin < 1.5 times the institutional upper limit of normal (ULN).

         14. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 (3 if liver
             metastases are present) times the institutional ULN.

         15. Lactate dehydrogenase ≤ 2 times the institutional ULN.

         16. The patient must have signed informed consent.

        Exclusion Criteria:

          1. Malignant melanoma that is uveal, mucosal, or acral.

          2. Patients who developed progressive disease within the first 8 weeks of their first
             treatment with a monoclonal antibody to PD-1 or PD-L1 with or without ipilimumab.

          3. Patients who have had more than 3 prior lines of therapy in the metastatic/advanced
             treatment setting.

          4. Patients with bone metastases, ≥3 visceral metastases (except lung or nodal metastases
             associated with visceral organs), any visceral metastasis >3 cm, or active cerebral
             metastases.

          5. 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.

          6. 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 registration.

          7. Therapeutic treatment with systemic antibiotics within 14 days of registration.

          8. Treatment with biologic therapy within 21 days of registration.

          9. Treatment with cytotoxic anticancer therapy within 21 days of registration.

         10. Treatment with wide-field radiation within 21 days of registration

         11. Prior treatment with an adenovirus-based gene therapy.

         12. Use of any investigational agents within 21 days of registration.

         13. The use of systemic immunostimulatory agents (including, but not limited to,
             interferons and IL2) are prohibited within 4 weeks or 5 half-lives of the drug
             (whichever is longer) prior to initiation of study treatment and during study
             treatment because these agents could potentially increase the risk for autoimmune
             conditions when given in combination with atezolizumab.

         14. Failed resolution/improvement of AEs including those related to anti-PD-1/anti-PD-L1
             back to grade 0-1 and requirement for treatment with >10 mg/day prednisone (or
             equivalent) for at least two weeks prior to registration.

         15. History of CTCAE grade 4 immune-related AEs from anti-PD-1/anti-PD-L1 antibody.

         16. History of CTCAE grade 4 AE that require steroid treatment (>10 mg/day prednisone or
             equivalent) for >12 weeks.

         17. Patients on warfarin are not eligible.

         18. 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 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
             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.

         19. Men who do not consent to the use of condoms during intercourse during study
             participation.

         20. Known active hepatitis B or C infection, or HIV infection.

         21. Patients with active, severe autoimmune disease or immune deficiency or previous
             Guillain-Barré syndrome. Patients with eczema, psoriasis, lichen simplex chronicus or
             vitiligo with dermatologic manifestations only (e.g., patients with psoriatic
             arthritis are excluded) are eligible for the study provided all of following
             conditions are met:

               1. Rash must cover <10% of body surface area.

               2. Disease is well-controlled at baseline and requires only low-potency topical
                  corticosteroids.

               3. Occurrence of acute exacerbations of the underlying condition requiring psoralen
                  plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral
                  calcineurin inhibitors, or high-potency or oral corticosteroids within the
                  previous 12 months.

         22. History of leptomeningeal disease.

         23. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
             drainage procedures (once monthly or more frequently).

         24. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
             obliterans), drug-induced pneumonitis or idiopathic pneumonitis, or evidence of active
             pneumonitis on screening chest computed tomography (CT) scan. However, history of
             radiation pneumonitis in the radiation field (fibrosis) is permitted.

         25. Unstable angina, uncontrolled cardiac arrhythmia, recent (within 3 months) history of
             myocardial infarction or stroke, or New York Class III/IV congestive heart failure.

         26. Major surgical procedure other than for the malignant melanoma diagnosis, within 4
             weeks prior to initiation of the study treatment, or anticipation of the need for a
             major surgical procedure during the study.

         27. Prior allogeneic stem cell or solid organ transplantation.

         28. History of severe allergic anaphylactic reactions to chimeric human or humanized
             antibodies, or fusion proteins.

         29. Known hypersensitivity to CHO cell products or any component of the atezolizumab
             formulation.

         30. Uncontrolled intercurrent illness including, but not limited to, psychiatric
             illness/social situations that in the opinion of the Investigator would compromise
             compliance to study requirements or put the patient at unacceptable risk.

         31. Other malignancy within the past 2 years (not including basal cell or squamous cell
             carcinoma of the skin, prostate cancer without the need of other treatment than
             hormones or in situ cervix, breast or melanoma).

         32. Live, attenuated vaccines (e.g., FluMist®) are prohibited within 4 weeks prior to
             initiation of study treatment, during treatment, and for 5 months after the final dose
             of atezolizumab and/or LOAd703.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients with toxicities
Time Frame:Up to 57 weeks post treatment initiation
Safety Issue:
Description:Tolerability is evaluated by the NCI CTCAE v5.0 based on interim medical history, physical examination and hematological and clinical chemistry laboratory studies

Secondary Outcome Measures

Measure:Overall response rate
Time Frame:Up to 57 weeks post treatment initiation
Safety Issue:
Description:Tumor size evaluations accordingly to RECIST 1.1
Measure:Overall survival
Time Frame:From treatment initiation post 12 months after last patients last visit
Safety Issue:
Description:Survival status of patients

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Lokon Pharma AB

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