Merkel Cell CarcinomaPhase 1NCT04160065
Immunotherapy With IFx-Hu2.0 Vaccine for Advanced Non-melanoma Skin Cancers
A Phase 1 study testing IFx-Hu2.0 in people with Merkel Cell Carcinoma and Cutaneous Squamous Cell Carcinoma, run by TuHURA Biosciences, Inc. at 4 sites in United States.
Trial summary
In this clinical phase I, non-randomized, open-label, uncontrolled, interventional, multi-center trial, 20 adult subjects (≥ 18 years of age) with advanced non-melanoma skin cancers will receive a fixed dose of 0.1 mg of IFx-Hu2.0 intralesionally as monotherapy in up to three lesions at up to three time points. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Merkel Cell Carcinoma, Cutaneous Squamous Cell Carcinoma, Non-Melanoma Skin Cancers
- What is being tested?
- IFx-Hu2.0
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 4 sitesUnited States
- Study dates
- 3 Mar 2020to 13 Aug 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Life expectancy ≥ 3 months at recruitment
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at the time of study treatment initiation.
- Males or females with histologically confirmed diagnosis of advanced non-melanoma skin cancers.
- Patients must have progressed despite standard therapy(ies) or are intolerant to or refused standard therapy(ies).
- Clinically measurable disease with at least 1 injectable lesion ≥ 3 mm in longest diameter; an injectable lesion is defined as an easily palpable superficial lesion (cutaneous, subcutaneous or lymph nodal metastasis) that can be accurately localized, stabilized by palpation, and is superficial enough to enable intralesional injection.
- No known bleeding diathesis or coagulopathy that would make intratumoral injection or biopsy unsafe
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- The entry laboratory criteria for subject eligibility must be less than or equal to Grade 1 adverse event levels for the parameters tested as defined by CTCAE v5.0:
- Bone Marrow Function:
- Hemoglobin (Hb) > LLN 10 g/dL
- White Blood Cell Count (WBC) > LLN 3,000 cells/mcL
- Platelet count (PLT) > LLN - 75,000 /mcL
- Blood Coagulation Parameters
- PT, INR < 1.5 x institutional ULN unless patient is therapeutically anticoagulated. If on anticoagulation PT/INR need to be within appropriate anticoagulation limits for the clinical indication. Patients who are receiving anticoagulants may participate in the trial if their anticoagulation can be stopped safely for several days at the time of biopsy.
- Renal Function
- Serum Creatinine (SCr) < 1 - 1.5 x baseline; < 1 1.5 x ULN
- Hepatic Function:
- Blood bilirubin < 1 - 1.5 x ULN if baseline was normal; < 1 1.5 x baseline if baseline was abnormal
- Serum Alanine Aminotransferase (ALT) < 1 - 3 x ULN if baseline was normal; 1.5 3 x baseline if baseline was abnormal
- Serum Aspartate Aminotransferase (AST) < 1 - 3 x ULN if baseline was normal; 1.5 3 x baseline if baseline was abnormal
- Alkaline Phosphatase (ALP) < 1 - 2.5 x ULN if baseline was normal; 2 2.5 x baseline if baseline was abnormal
- Gamma Glutylamyltransferase (GGT) < 1 - 2.5 x ULN, if baseline was normal; 2 2.5 x baseline if baseline was abnormal
- Males and females of reproductive potential must agree to continuously use adequate contraception prior to study entry and for up to 6 months thereafter. A female is of childbearing potential unless she has had a surgical procedure that would accomplish sterility such a bilateral tubal ligation, hysterectomy or has not had menses for the past 12 months.
- Females of childbearing potential must have a negative urine or serum pregnancy test within one week prior to start of treatment
- Patient or legal representative must understand and sign a written informed consent form.
Who cannot join
- Concurrent use of any other investigational product or participation in another trial within 28 days before start of study treatment.
- Have received oncologic therapy within 2 weeks of planned IFx-Hu2.0 injection
- Presence or history of central nervous system metastasis [treated/stable brain metastasis are allowable when patients have received prior therapy for their brain metastases and their central nervous system (CNS) disease is radiographically stable (> 4 weeks)]
- Pregnant or breastfeeding females and females desiring to become pregnant or breastfeed within the timeframe of this study
- Concurrent steroid therapy (> 10 mg of daily prednisone equivalent) or other immunosuppressive therapies such as those needed for solid organ transplants and rheumatoid arthritis. Topical or inhaled steroids are allowable.
- History of organ allograft transplantation
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- History of hemolytic anemia
- History of significant tumor bleeding, or coagulation or bleeding disorders.
- Patients with autoimmune disorder, with exception of patients with vitiligo or endocrine-related autoimmune conditions receiving appropriate hormonal supplementation who are eligible; systemic use of immunosuppressant drugs such as steroids (except as hormone replacement therapy or short-course supportive medication such as chemotherapy or drug allergy, etc.), azathioprine, tacrolimus, cyclosporine, etc. within 4 weeks before recruitment. Prior autoimmune toxicity resolved to Grade 1 or less no longer requiring immunosuppressive therapy is not an exclusion under this criterion.
- Major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered major surgery) resulting from a prior surgery
- Leptomeningeal involvement regardless of treatment status
- Active, clinically serious uncontrolled medical conditions such as HIV, HBV, HCV, and EBV infection
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with protocol requirements
- Unwilling or unable to follow protocol requirements
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: Phase 1 Trial of Intralesional Immunotherapy With IFx-Hu2.0 Vaccine in Patients With Advanced Non-melanoma Skin Cancers
In this clinical phase I, non-randomized, open-label, uncontrolled, interventional, multi-center trial, 20 adult subjects (≥ 18 years of age) with advanced non-melanoma skin cancers will receive a fixed dose of 0.1 mg of IFx-Hu2.0 intralesionally as monotherapy in up to three lesions at up to three time points. Subjects will be observed for any acute adverse events (AEs) post injection and for any delayed AEs at Day 28, 35 and/or 42 ± 7 days, depending on the cohort (exposure escalation and expansion design).
Read the detailed description
Approximately twenty adult patients (≥ 18 years of age), of any sex, ethnicity, and race with histologically confirmed advanced non-melanoma skin cancers with accessible lesions, will be eligible for study enrollment and treatment with IFx-Hu2.0 (i.e. 20 total patients across both indications). These types of advanced non-melanoma skin cancers are very rare in the pediatric population (< 18 years of age) with only scattered case reports. The potential for development of this product for pediatric subjects with non-melanoma skin cancers will be evaluated after the results of this study are available.
Patients must have at least one injectable lesion, defined as an easily palpable superficial lesion (cutaneous, subcutaneous or lymph nodal metastasis) that can be accurately localized, stabilized by palpation, and is superficial enough to enable intralesional injection.
To be eligible for this study, patients must have progressed despite standard therapy(ies), or are intolerant to or refused standard therapy(ies).
Enrollees will receive IFx-Hu2.0 as a monotherapy at up to three-time points. Depending on the number of accessible lesions, a patient could receive up to three doses across three lesions (one dose per lesion). The maximum number of lesions to be injected at any time point under this protocol is three lesions. Blood will be collected from these patients prior to treatment administration at every drug administration visit. These samples will be used to perform CBC and clinical chemistry tests. A urine sample will be obtained for urinalysis for protein and blood at the same frequency. Blood samples will also be drawn at the same intervals for immune response evaluation as well.
This is primarily a safety study that is designed to evaluate IFx-Hu2.0 monotherapy and provide foundational evidence to potentially support further studies investigating IFx-Hu2.0 + anti-PD-1 combination therapy for patients with non-melanoma skin cancers.
- Being tested
- IFx-Hu2.0
- Keywords
- Advanced, MCC, cSCC, pDNA, plasmid DNA, pAc/emm55, Gene Therapy, Immuno-Oncology, Therapeutic Cancer Vaccine, Immunotherapy
- Medical subject headings
- Carcinoma, Merkel Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IFx-Hu2.0Biological
Also called pAc/emm55
The investigational drug product IFx-Hu2.0 is composed of the drug substance pAc/emm55 (pDNA) complexed with the two excipients in vivo-jetPEI® (linear polyethylenimine), a transfection reagent, and dextrose, a pDNA/polyethylenimine complex stabilizer.
Therapeutic Classification:
- Immunomodulatory Agent
Route of Administration:
- Intralesional (i.e. injection of cutaneous, subcutaneous or nodal lesions)
Mechanism of Action:
- Injection of IFx-Hu2.0 into the lesion facilitates the expression of the immunogenic Emm55 protein by the tumor cells.
Physiological Effect:
- Expression of the emm55 gene by the tumor cells triggers immune recognition of tumor-specific and -associated antigens which leads to innate and adaptive immune responses.
| Study group | Role | What they receive |
|---|---|---|
| IFx-Hu2.0 (plasmid DNA) 0.1 mg/lesion/time point | Experimental | Exposure Escalation:
* The first 3 subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at a single time point (28-day follow-up post last injection); 3/3 patients recruited.
* The second 3 subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at 2 time points 7 days apart (28-day follow-up post last injection); 1/3 patients recruited.
* The third 3 subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at 3 time points 7 days apart (28-day follow-up post last injection); recruitment pending.
Cohort Expansion:
* The remaining 11 subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at 3 time points 7 days apart (28-day follow-up post last injection); recruitment pending. Receives: Biological: IFx-Hu2.0 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Grade 3-5, Treatment-Related Adverse Events per CTCAE 5.0
Measured: 28 days from last injection
Secondary outcomes (3)
Number of Enrolled Subjects who have completed the Trial without Major Protocol Deviations
Measured: 28 days from last injection
Objective Response Rate (ORR) per 2018 FDA Guidance on Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics
Measured: 28 days from last injection
Best Overall Response per RECIST v1.1
Measured: 28 days from last injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2019
- Study start3 Mar 2020
- Primary completion19 Oct 2023
- Study completion13 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Merkel Cell CarcinomaStudies 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- TuHURA Biosciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- H. Lee Moffitt Cancer Center and Research Institute, University of Southern California, Dana-Farber Cancer Institute, Huntsman Cancer Institute
- Responsible party
- Sponsor
- Investigators
- Andrew S Brohl, MD, Principal investigator, Collaborator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04160065
- Sponsor's protocol ID
- NMSC 2019-01
- Status last verified
- Sep 2024
- First submitted
- 7 Nov 2019
- Last updated
- 23 Sep 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Trial of Intralesional Immunotherapy With IFx-Hu2.0 Vaccine in Patients With Advanced Non-melanoma Skin Cancers
- ClinicalTrials.gov ID
- NCT04160065
- Acronym / sponsor ID
- NMSC 2019-01
- Keywords
- Advanced, MCC, cSCC, pDNA, plasmid DNA, pAc/emm55, Gene Therapy, Immuno-Oncology
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- TuHURA Biosciences, Inc.Industry (pharma, biotech, devices)
- Collaborators
- H. Lee Moffitt Cancer Center and Research Institute, University of Southern California, Dana-Farber Cancer Institute, Huntsman Cancer Institute
- Study start
- 3 Mar 2020 (actual)
- Primary completion
- 19 Oct 2023 (actual)
- Study completion
- 13 Aug 2024 (actual)
- First posted
- 12 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this clinical phase I, non-randomized, open-label, uncontrolled, interventional, multi-center trial, 20 adult subjects (≥ 18 years of age) with advanced non-melanoma skin cancers will receive a fixed dose of 0.1 mg of IFx-Hu2.0 intralesionally as monotherapy in up to three lesions at up to three time points. Subjects will be observed for any acute adverse events (AEs) post injection and for any delayed AEs at Day 28, 35 and/or 42 ± 7 days, depending on the cohort (exposure escalation and expansion design).
Detailed description
Approximately twenty adult patients (≥ 18 years of age), of any sex, ethnicity, and race with histologically confirmed advanced non-melanoma skin cancers with accessible lesions, will be eligible for study enrollment and treatment with IFx-Hu2.0 (i.e. 20 total patients across both indications). These types of advanced non-melanoma skin cancers are very rare in the pediatric population (< 18 years of age) with only scattered case reports. The potential for development of this product for pediatric subjects with non-melanoma skin cancers will be evaluated after the results of this study are available.
Patients must have at least one injectable lesion, defined as an easily palpable superficial lesion (cutaneous, subcutaneous or lymph nodal metastasis) that can be accurately localized, stabilized by palpation, and is superficial enough to enable intralesional injection.
To be eligible for this study, patients must have progressed despite standard therapy(ies), or are intolerant to or refused standard therapy(ies).
Enrollees will receive IFx-Hu2.0 as a monotherapy at up to three-time points. Depending on the number of accessible lesions, a patient could receive up to three doses across three lesions (one dose per lesion). The maximum number of lesions to be injected at any time point under this protocol is three lesions. Blood will be collected from these patients prior to treatment administration at every drug administration visit. These samples will be used to perform CBC and clinical chemistry tests. A urine sample will be obtained for urinalysis for protein and blood at the same frequency. Blood samples will also be drawn at the same intervals for immune response evaluation as well.
This is primarily a safety study that is designed to evaluate IFx-Hu2.0 monotherapy and provide foundational evidence to potentially support further studies investigating IFx-Hu2.0 + anti-PD-1 combination therapy for patients with non-melanoma skin cancers.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IFx-Hu2.0 (plasmid DNA) 0.1 mg/lesion/time point | Experimental | Biological: IFx-Hu2.0Exposure Escalation: * The first 3 subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at a single time point (28-day follow-up post last injection); 3/3 patients recruited. * The second 3 subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at 2 time points 7 days apart (28-day follow-up post last injection); 1/3 patients recruited. * The third 3 subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at 3 time points 7 days apart (28-day follow-up post last injection); recruitment pending. Cohort Expansion: * The remaining 11 subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at 3 time points 7 days apart (28-day follow-up post last injection); recruitment pending. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Life expectancy ≥ 3 months at recruitment
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 at the time of study treatment initiation.
- Males or females with histologically confirmed diagnosis of advanced non-melanoma skin cancers.
- Patients must have progressed despite standard therapy(ies) or are intolerant to or refused standard therapy(ies).
- Clinically measurable disease with at least 1 injectable lesion ≥ 3 mm in longest diameter; an injectable lesion is defined as an easily palpable superficial lesion (cutaneous, subcutaneous or lymph nodal metastasis) that can be accurately localized, stabilized by palpation, and is superficial enough to enable intralesional injection.
Key exclusion criteria (14 listed)
- Concurrent use of any other investigational product or participation in another trial within 28 days before start of study treatment.
- Have received oncologic therapy within 2 weeks of planned IFx-Hu2.0 injection
- Presence or history of central nervous system metastasis [treated/stable brain metastasis are allowable when patients have received prior therapy for their brain metastases and their central nervous system (CNS) disease is radiographically stable (> 4 weeks)]
- Pregnant or breastfeeding females and females desiring to become pregnant or breastfeed within the timeframe of this study
- Concurrent steroid therapy (> 10 mg of daily prednisone equivalent) or other immunosuppressive therapies such as those needed for solid organ transplants and rheumatoid arthritis. Topical or inhaled steroids are allowable.
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 |
|---|---|---|
| IFx-Hu2.0Also: pAc/emm55The investigational drug product IFx-Hu2.0 is composed of the drug substance pAc/emm55 (pDNA) complexed with the two excipients in vivo-jetPEI® (linear polyethylenimine), a transfection reagent, and dextrose, a pDNA/polyethylenimine complex stabilizer. Therapeutic Classification: * Immunomodulatory Agent Route of Administration: * Intralesional (i.e. injection of cutaneous, subcutaneous or nodal lesions) Mechanism of Action: * Injection of IFx-Hu2.0 into the lesion facilitates the expression of the immunogenic Emm55 protein by the tumor cells. Physiological Effect: * Expression of the emm55 gene by the tumor cells triggers immune recognition of tumor-specific and -associated antigens which leads to innate and adaptive immune responses. | Biological | IFx-Hu2.0 (plasmid DNA) 0.1 mg/lesion/time point |
Primary outcome
Number of Grade 3-5, Treatment-Related Adverse Events per CTCAE 5.0
Time frame: 28 days from last injection
3 secondary outcomes
Number of Enrolled Subjects who have completed the Trial without Major Protocol Deviations
Time frame: 28 days from last injection
Objective Response Rate (ORR) per 2018 FDA Guidance on Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics
Time frame: 28 days from last injection
Best Overall Response per RECIST v1.1
Time frame: 28 days from last injection
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2024.
- 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.
Andrew S Brohl, MD principal investigator
Collaborator
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IFx-Hu2.0 in people with Merkel Cell Carcinoma and Cutaneous Squamous Cell Carcinoma, run by TuHURA Biosciences, Inc. at 4 sites in United States.
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 24 inclusion and 14 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 23 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 4 sites in United States. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of Grade 3-5, Treatment-Related Adverse Events per CTCAE 5.0 (time frame: 28 days from last injection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Sep 2024.