A Phase I/II Trial Investigating LOAd703 in Combination With Atezolizumab in Malignant Melanoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04123470|
Recruitment Status : Recruiting
First Posted : October 11, 2019
Last Update Posted : April 6, 2022
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
|Condition or disease||Intervention/treatment||Phase|
|Malignant Melanoma||Genetic: delolimogene mupadenorepvec Biological: atezolizumab||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||35 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Trial Investigating LOAd703 in Combination With Atezolizumab in Malignant Melanoma|
|Actual Study Start Date :||January 28, 2020|
|Estimated Primary Completion Date :||June 30, 2023|
|Estimated Study Completion Date :||June 30, 2024|
Delolimogene mupadenorepvec plus atezolizumab
Genetic: delolimogene mupadenorepvec
LOAd703 is an oncolytic adenovirus encoding TMZ-CD40L and 4-1BBL
Other Name: LOAd703
Atezolizumab is an anti-PD-L1 antibody
- Number of patients with toxicities [ Time Frame: Up to 57 weeks post treatment initiation ]Tolerability is evaluated by the NCI CTCAE v5.0 based on interim medical history, physical examination and hematological and clinical chemistry laboratory studies
- Overall response rate [ Time Frame: Up to 57 weeks post treatment initiation ]Tumor size evaluations accordingly to RECIST 1.1
- Overall survival [ Time Frame: From treatment initiation post 12 months after last patients last visit ]Survival status of patients
- Antibodies against LOAd703 [ Time Frame: Up to 57 weeks post treatment initiation ]Number of antibodies targeting adenovirus (LOAd703) in serum
- Immune cell phenotype [ Time Frame: Up to 57 weeks post treatment initiation ]Presence of immune cells (MFI) in blood and their fold change over time compared to baseline as determined by flow cytometry
- Virus shedding [ Time Frame: Up to 57 weeks post treatment initiation ]Number of detected virus particles are evaluated in blood, urine, oral and rectal swabs
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- The patient must have signed informed consent.
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04123470
|United States, California|
|Cedars-Sinai Medical Center, The Angeles Clinic and Research Institute||Recruiting|
|Los Angeles, California, United States, 90025|
|Contact: Omar Hamid, MD 310-582-7900 email@example.com|
|United States, Texas|
|Baylor St Luke's Medical Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Daniel Wang, MD 713-798-3750 firstname.lastname@example.org|
|Uppsala University Hospital||Recruiting|
|Uppsala, Sweden, 75185|
|Contact: Annika Liden, nurse 018-6110000 email@example.com|
|Contact: Gustav Ullenhag, MD PhD 018-6110000|
|Study Chair:||Angelica Loskog, PhD||Lokon Pharma AB|
|Responsible Party:||Lokon Pharma AB|
|Other Study ID Numbers:||
2019-003300-12 ( EudraCT Number )
|First Posted:||October 11, 2019 Key Record Dates|
|Last Update Posted:||April 6, 2022|
|Last Verified:||April 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas