Non Small Cell Lung CancerPhase 1NCT03689192
Arginase-1 Peptide Vaccine in Patients With Metastatic Solid Tumors
A Phase 1 study testing ARG1-18,19,20 in people with Non Small Cell Lung Cancer and Urothelial Carcinoma, run by Herlev Hospital at 1 site in Denmark.
Trial summary
In this phase I first-in-humans-study a vaccine consisting of arginase-1 (ARG1) peptides and the adjuvant Montanide ISA-51 will be tested in ten patients with metastatic solid tumors. Patients will be treated with an ARG1 vaccine every third week for 45 weeks. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer, Urothelial Carcinoma, Malignant Melanoma
- What is being tested?
- ARG1-18,19,20
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteDenmark
- Study dates
- 17 Dec 2018to 19 Jan 2022
- Phase
- Phase 1
- 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
- Age ≥ 18
- The patient has metastatic solid tumors (NSCLC, colorectal cancer, urothelial cancer, breast cancer, ovarian cancer, malignant melanoma or HNSCC); progressive or recurrent disease on or following treatment with standard of care agents
- At least one measurable parameter according to RECIST 1.1.
- The patient has an ECOG performance status of 0 or 1
- Life expectancy of at least 3 months
- Prior PD1/PD-L1 allowed
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- The patient is a female of childbearing potential with negative pregnancy test
- For fertile women: Agreement to use contraceptive methods with a failure rate of < 1 % per year during the treatment period and for at least 150 days 12 weeks after the treatment. Safe contraceptive methods for women are birth control pills, intrauterine device, contraceptive injection, contraceptive implant, contraceptive patch or contraceptive vaginal ring.
- For men: Agreement to use contraceptive measures and agreement to refrain from donating sperm
- The patient has met the following hematological and biochemical criteria:
- AST and ALT ≤2,5 X ULN or ≤5 X ULN with liver metastases
- Serum total bilirubin ≤1,5 X ULN or direct bilirubin ≤ ULN for patient with total bilirubin level > 1,5 ULN
- Serum creatinine ≤1,5 X ULN
- ANC (Absolute Neutrophil Count) ≥1,000/mcL
- Platelets ≥ 75,000 /mcL
- Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L
- Mandatory provision of archival tissue and blood for biomarker testing at baseline
- Mandatory provision of blood for biomarker testing during the study
- Signed declaration of consent after oral and written information about the protocol
Who cannot join
- The patient has not recovered from surgery or is less than 4 weeks from major surgery
- The patient has a history of life-threatening or severe immune related adverse events on treatment with another immunotherapy and is considered to be at risk of not recovering
- The patient is expected to require any other form of systemic antineoplastic therapy or radiation therapy while receiving the treatment. However, radiation therapy treatment of non target lesion is allowed.
- The patient has a history of severe clinical autoimmune disease
- The patient has a history of pneumonitis, organ transplant, human immunodeficiency virus positive, active hepatitis B or hepatitis C
- The patient requires systemic steroids for management of immune-related adverse events experienced on another immunotherapy
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- The patient has any condition that will interfere with patient compliance or safety (including but not limited to psychiatric or substance abuse disorders)
- The patient is pregnant or breastfeeding
- The patient is unable to voluntarily agree to participate by signed informed consent or assent
- The patient has an active infection requiring systemic therapy
- The patient has received a live virus vaccine within 30 days of planned start of therapy
- Significant medical disorder according to investigator; e.g. severe asthma or chronic obstructive lung disease, dysregulated heart disease or dysregulated diabetes mellitus
- Concurrent treatment with other experimental drugs
- Concurrent treatment with Valproate or Xanthin Oxidase inhibitors
- Known side effects to Montanide ISA-51
- Any active autoimmune diseases e.g. autoimmune neutropenia, thrombocytopenia or hemolytic anemia, systemic lupus erythematosus, scleroderma, myasthenia gravis, autoimmune glomerulonephritis, autoimmune adrenal deficiency, autoimmune thyroiditis etc.
- Severe allergy or anaphylactic reactions earlier in life
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Center for Cancer Immune Therapy Dept. of Hematology/oncology
Copenhagen, Herlev, 2730
About this study
In this phase I first-in-humans-study a vaccine consisting of arginase-1 (ARG1) peptides and the adjuvant Montanide ISA-51 will be tested in ten patients with metastatic solid tumors. Patients will be treated with an ARG1 vaccine every third week for 45 weeks.
Read the detailed description
Arginase-1 (ARG1) is an enzyme that converts the amino acid arginine into urea and ornithine. ARG1 is mainly expressed in hepatocytes but different myeloid cells are also capable of ARG1-expression.
An ARG1-induced arginine depletion suppresses T cell function through the impairment of the T cell receptor (TCR)-complex. A research group from the Center for Cancer Immune Therapy (CCIT) have identified spontaneous T cell reactivity against ARG1 peptides in peripheral blood mononuclear cells of cancer patients and healthy donors. The theoretic background for an ARG1 peptide vaccine is to activate ARG1-specific T cells to infiltrate the tumor microenvironment and eliminate ARG1-expressing immunosuppressive cells. The aim is to treat 10 patients with progressive solid tumors following treatment with standard of care agents. Patients will receive ARG1 vaccinations administered subcutaneously every third week for 45 weeks.
The primary endpoint is to evaluate safety and toxicity. Immune responses will be assessed using blood- and tumor tissue samples and clinical responses are evaluated using RECIST 1.1.
- Conditions
- Non Small Cell Lung Cancer, Urothelial Carcinoma, Malignant Melanoma, Ovarian Cancer, Colorectal Cancer, Breast Cancer
- Being tested
- ARG1-18,19,20
- Keywords
- Arginase 1
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Carcinoma, Transitional Cell, Melanoma, Ovarian Neoplasms, Colorectal Neoplasms, Breast Neoplasms, Squamous Cell Carcinoma of Head and Neck, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARG1-18,19,20Biological
300 ug ARG1-18,19,20 peptide in water mixed with 500ul montanide
| Study group | Role | What they receive |
|---|---|---|
| ARG1-18,19,20 peptide vaccine | Experimental | One ARG1-vaccine every third week for 45 weeks. Receives: Biological: ARG1-18,19,20 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Events Evaluated by CTCAE 4.0
Patients were evaluated according to Common Terminology Criteria for Adverse Events (CTCEA). An adverse event (AE) is an abnormal clinical finding. Each participant was assessed from start of treatment until 6 months after the last vaccine.
Measured: 0 - 75 weeks
Secondary outcomes (3)
Immune Responses
To evaluate the immunological impact of the ARG1-18,19,20 peptide vaccines using blood samples and tumor biopsies.
Measured: project blood samples were taken at baseline and every 3 months for a maximum of 1,5 year. Tumor biopsies were taken at baseline and after 3 months if possible.
Overall Survival
Overall Survival (OS) defined as time from treatment initiation to death, will be described with use of Kaplan Meier curve.
Measured: 0 - 75 weeks
4.Progression Free Survival
Progression free survival (PFS) defined as the time from treatment initiation to disease progression, relapse or death due to any cause, which ever comes first, will be described with Kaplan Meier curve.
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: 0 - 75 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2018
- Study start17 Dec 2018
- Primary completion19 Jan 2022
- Study completion19 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Herlev Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Inge Marie Svane, Herlev Hospital
- Investigators
- Inge Marie Svane, Prof., MD, Study director, CCIT-DK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03689192
- Sponsor's protocol ID
- AA1809
- Status last verified
- Feb 2023
- First submitted
- 27 Sep 2018
- Last updated
- 28 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lorentzen CL, Martinenaite E, Kjeldsen JW, Holmstroem RB, Mork SK, Pedersen AW, Ehrnrooth E, Andersen MH, Svane IM. Arginase-1 targeting peptide vaccine in patients with metastatic solid tumors - A phase I trial. Front Immunol. 2022 Oct 17;13:1023023. doi: 10.3389/fimmu.2022.1023023. eCollection 2022.
PubMed 36330525
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Arginase-1 Peptide Vaccine in Patients With Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT03689192
- Acronym / sponsor ID
- AA1809
- Conditions
- Non Small Cell Lung Cancer, Urothelial Carcinoma, Malignant Melanoma, Ovarian Cancer, Colorectal Cancer, Breast Cancer
- Keywords
- Arginase 1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Herlev HospitalUniversity, hospital or other
- Study start
- 17 Dec 2018 (actual)
- Primary completion
- 19 Jan 2022 (actual)
- Study completion
- 19 Jan 2022 (actual)
- First posted
- 28 Sep 2018 (actual)
- Results
- Posted 28 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this phase I first-in-humans-study a vaccine consisting of arginase-1 (ARG1) peptides and the adjuvant Montanide ISA-51 will be tested in ten patients with metastatic solid tumors. Patients will be treated with an ARG1 vaccine every third week for 45 weeks.
Detailed description
Arginase-1 (ARG1) is an enzyme that converts the amino acid arginine into urea and ornithine. ARG1 is mainly expressed in hepatocytes but different myeloid cells are also capable of ARG1-expression.
An ARG1-induced arginine depletion suppresses T cell function through the impairment of the T cell receptor (TCR)-complex. A research group from the Center for Cancer Immune Therapy (CCIT) have identified spontaneous T cell reactivity against ARG1 peptides in peripheral blood mononuclear cells of cancer patients and healthy donors. The theoretic background for an ARG1 peptide vaccine is to activate ARG1-specific T cells to infiltrate the tumor microenvironment and eliminate ARG1-expressing immunosuppressive cells. The aim is to treat 10 patients with progressive solid tumors following treatment with standard of care agents. Patients will receive ARG1 vaccinations administered subcutaneously every third week for 45 weeks.
The primary endpoint is to evaluate safety and toxicity. Immune responses will be assessed using blood- and tumor tissue samples and clinical responses are evaluated using RECIST 1.1.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ARG1-18,19,20 peptide vaccine | Experimental | Biological: ARG1-18,19,20One ARG1-vaccine every third week for 45 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Age ≥ 18
- The patient has metastatic solid tumors (NSCLC, colorectal cancer, urothelial cancer, breast cancer, ovarian cancer, malignant melanoma or HNSCC); progressive or recurrent disease on or following treatment with standard of care agents
- At least one measurable parameter according to RECIST 1.1.
- The patient has an ECOG performance status of 0 or 1
- Life expectancy of at least 3 months
Key exclusion criteria (17 listed)
- The patient has not recovered from surgery or is less than 4 weeks from major surgery
- The patient has a history of life-threatening or severe immune related adverse events on treatment with another immunotherapy and is considered to be at risk of not recovering
- The patient is expected to require any other form of systemic antineoplastic therapy or radiation therapy while receiving the treatment. However, radiation therapy treatment of non target lesion is allowed.
- The patient has a history of severe clinical autoimmune disease
- The patient has a history of pneumonitis, organ transplant, human immunodeficiency virus positive, active hepatitis B or hepatitis C
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ARG1-18,19,20300 ug ARG1-18,19,20 peptide in water mixed with 500ul montanide | Biological | ARG1-18,19,20 peptide vaccine |
Primary outcome
Adverse Events Evaluated by CTCAE 4.0
Time frame: 0 - 75 weeks
Patients were evaluated according to Common Terminology Criteria for Adverse Events (CTCEA). An adverse event (AE) is an abnormal clinical finding. Each participant was assessed from start of treatment until 6 months after the last vaccine.
3 secondary outcomes
Immune Responses
Time frame: project blood samples were taken at baseline and every 3 months for a maximum of 1,5 year. Tumor biopsies were taken at baseline and after 3 months if possible.
Overall Survival
Time frame: 0 - 75 weeks
4.Progression Free Survival
Time frame: 0 - 75 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36330525Lorentzen CL, Martinenaite E, Kjeldsen JW, Holmstroem RB, Mork SK, Pedersen AW, Ehrnrooth E, Andersen MH, Svane IM. Arginase-1 targeting peptide vaccine in patients with metastatic solid tumors - A phase I trial. Front Immunol. 2022 Oct 17;13:1023023. doi: 10.3389/fimmu.2022.1023023. eCollection 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Inge Marie Svane, Prof., MD study director
CCIT-DK
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ARG1-18,19,20 in people with Non Small Cell Lung Cancer and Urothelial Carcinoma, run by Herlev Hospital at 1 site in Denmark.
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 19 inclusion and 17 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 28 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. 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 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.
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 28 Feb 2023). 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?
Adverse Events Evaluated by CTCAE 4.0 (time frame: 0 - 75 weeks). 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 NCT03689192, which also lists 1 linked publication.
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 28 Feb 2023.