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Malignant MelanomaPhase 1/2NCT04123470

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

A Phase 1/2 study testing delolimogene mupadenorepvec and atezolizumab in people with Malignant Melanoma, run by Lokon Pharma AB at 3 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Melanoma
What is being tested?
delolimogene mupadenorepvec and atezolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
3 sitesin 2 countries
Study dates
28 Jan 2020to 30 Jul 2023
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • The patient must have signed informed consent.

Who cannot join

  • 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.
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  • 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 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).
  • 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 18.
  • Known active hepatitis B or C infection, or HIV infection.
  • 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:
  • Rash must cover <10% of body surface area.
  • Disease is well-controlled at baseline and requires only low-potency topical corticosteroids.
  • 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.
  • History of leptomeningeal disease.
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
  • 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 or tested reduced functional respiration capacity. However, history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Unstable angina, uncontrolled cardiac arrhythmia, recent (within 3 months) history of myocardial infarction or stroke, or New York Class III/IV congestive heart failure.
  • 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.
  • Prior allogeneic stem cell or solid organ transplantation.
  • History of severe allergic anaphylactic reactions to chimeric human or humanized antibodies, or fusion proteins.
  • Known hypersensitivity to CHO cell products or any component of the atezolizumab formulation.
  • 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.
  • 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).
  • 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.

Trial locations and contacts

3 sites in 2 countries.

3 sites in 2 countries

United States2 sites

  • Baylor St Luke's Medical Center

    Houston, Texas, 77030

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

    Los Angeles, California, 90025

Other trials in United States

Sweden1 site

  • Uppsala University Hospital

    Uppsala, 75185

Other trials in Sweden

About this study

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.

Read the 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.

Being tested
delolimogene mupadenorepvec, atezolizumab
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • delolimogene mupadenorepvecGenetic

    Also called LOAd703

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

  • atezolizumabBiological

    Atezolizumab is an anti-PD-L1 antibody

Study groups in NCT04123470
Study groupRoleWhat they receive
TreatmentExperimentalDelolimogene mupadenorepvec plus atezolizumab
Receives: Genetic: delolimogene mupadenorepvec; Biological: atezolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Up to 57 weeks post treatment initiation

Secondary outcomes (6)

  1. Overall Response Rate

    Tumor size evaluations accordingly to RECIST 1.1.Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable disease (SD), Neither PR nor progressive disease, Progressive disease (PD), >20% increase in the sum of the longest diameter of target lesions. Overall Response (OR) = number of participants with CR or PR.

    Measured: Up to 57 weeks post treatment initiation

  2. Overall Survival

    Survival status of patients. Overall survival is defined as the time from the first dose of study treatment (LOAd703 and/or atezolizumab) until death.

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

  3. Antibodies Against LOAd703

    Fold change between baseline and evaluation visit for anti-adenovirus antibodies (LOAd703).

    The baseline is the last available measurement taken before the first LOAd703 treatment. Evaluation is a measurement taken from subjects receiving at least 3 LOAd703 treatments.

    Measured: Up to 57 weeks post treatment initiation

  4. Immune Cell Phenotype

    The ratio for CD8+/Treg cells analyzed in blood at baseline and evaluation visit as determined by flow cytometry.

    The baseline is the last available measurement taken before the first LOAd703 treatment. Evaluation is a measurement taken from subjects receiving at least 3 LOAd703 treatments.

    Measured: Up to 57 weeks post treatment initiation

  5. Virus Shedding

    Number of samples analyzed that were positive for virus particles in shedding samples.

    Measured: Up to 57 weeks post treatment initiation

  6. Overall Survival (Number of Participants With Event)

    Survival status of patients described by number of participants with event.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Oct 2019
  2. Study start28 Jan 2020
  3. Primary completion30 Jul 2023
  4. Study completion30 Jul 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
Participants treated with LOAd703 at two dose levels (1x10e11 VP and 5x10e11VP) and fixed dose of atezolizumab
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04123470
Sponsor's protocol ID
LOKON003
Other IDs
2019-003300-12, 2019
Status last verified
Sep 2024
First submitted
9 Oct 2019
Last updated
19 Sep 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Grauers Wiktorin H, Ekstrom-Ryden V, Ek I, Eriksson E, Lovgren T, Bernedal Nordstrom C, Sandin LC, Patel MR, Hamid O, Ullenhag G, Loskog A. Reprogramming myeloid cells and restoring T cell fitness in checkpoint inhibitor resistant melanoma patients. Biomark Res. 2026 Mar 27;14(1):38. doi: 10.1186/s40364-026-00917-z.

    PubMed 41888981

  • Hamid O, Ekstrom-Ryden V, Mehmi I, Wang D, Patel M, Alsaqal S, Irenaeus S, Nordstrom C, Sandin LC, Grauers Wiktorin H, Lovgren T, Eriksson E, Leja-Jarblad J, Loskog A, Ullenhag GJ. LOAd703-induced tumor microenvironment gene engineering in combination with atezolizumab in metastatic malignant melanoma: a phase I/II trial. Nat Commun. 2026 Feb 16;17(1):1760. doi: 10.1038/s41467-026-69629-0.

    PubMed 41698954

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing delolimogene mupadenorepvec and atezolizumab in people with Malignant Melanoma, run by Lokon Pharma AB at 3 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Tolerability Evaluated by NCI CTCAE v5.0 (time frame: Up to 57 weeks post treatment initiation). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04123470, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.

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