Metastatic MelanomaPhase 1PelicanNCT03773744
MG1-MAGEA3 With Ad-MAGEA3 and Pembrolizumab in Patients With Previously Treated Metastatic Melanoma or Cutaneous Squamous Cell Carcinoma
A Phase 1 study testing Ad-MAGEA3, MG1-MAGEA3 and Pembrolizumab in people with Metastatic Melanoma and Squamous Cell Skin Carcinoma, run by Turnstone Biologics, Corp..
Trial summary
This is a Phase 1b open-label dose escalation trial of Ad/MG1-MAGEA3 and Pembrolizumab in patients with Metastatic Melanoma or Cutaneous Squamous Cell Skin Cancer that has failed prior standard of care treatments. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma, Squamous Cell Skin Carcinoma
- What is being tested?
- Ad-MAGEA3, MG1-MAGEA3 and Pembrolizumab
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 15 Feb 2020to 31 Dec 2021
- 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
- Have histologically or cytologically confirmed diagnosis of locally advanced metastatic melanoma or cutaneous squamous cell carcinoma that has failed standard therapies
- For patients treated intratumorally, must have a lesion suitable for direct injection of MG1-MAGEA3
- Have at least one tumor amenable to biopsy
- Have measurable disease via RECIST 1.1 criteria
- Adequate organ function and performance status
- Additional inclusion criteria present
Who cannot join
- Prior treatment with any MAGE-A3 vaccine immunotherapy
- Prior systemic therapy for cancer within 4 weeks (8 weeks for lung radiation), and has recovered from chemo-related toxicities to Grade 1 or less
- Intolerant to prior PD1/PD-L1 therapy
- Requires use of anti-platelet or anti-coagulant therapy that cannot be safely suspended for per protocol biopsies or intra-tumoral injections.
- Known active CNS metastases and/or carcinomatous meningitis.
- Active autoimmune disease that has required systemic therapy in the past 2 years.
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- Conditions likely to have resulted in splenic dysfunction.
- Known HIV/AIDS, active HBV or HCV infection.
- Additional Exclusion criteria exist
About this study
Official title: A Phase 1b, Multicenter, Open-label Trial of Oncolytic MG1 Expressing MAGE-A3 (MG1-MAGEA3) With Adenovirus Vaccine Expressing MAGE-A3 (Ad-MAGEA3), in Combination With Immune Modulating Therapy in Patients With Metastatic Melanoma or Previously Treated Cutaneous Squamous Cell Carcinoma
This is a Phase 1b open-label dose escalation trial of Ad/MG1-MAGEA3 and Pembrolizumab in patients with Metastatic Melanoma or Cutaneous Squamous Cell Skin Cancer that has failed prior standard of care treatments. Upon determination of a Maximum Tolerated Dose (MTD) or Maximum Feasible Dose (MFD) the study will be expanded into up to 24 additional Metastatic Melanoma patients.
Read the detailed description
This is a Phase 1b open-label dose escalation trial of Ad/MG1-MAGEA3 and Pembrolizumab in patients with Metastatic Melanoma or Cutaneous Squamous Cell Skin Cancer that has failed prior standard of care treatments. This study will consist of two arms where the dose will be increased independently until the maximum tolerated dose (MTD) / maximum feasible dose (MFD) is reached.
Arm 1 - Low-dose cyclophosphamide, followed by an Ad-MAGEA3 intramuscular (IM) prime, followed by intravenous (IV) administration of MG1-MAGEA3 and IV pembrolizumab.
Arm 2 - Ad-MAGEA3 IM injection as a prime, followed by IV administration of MG1-MAGEA3, followed by intratumoral (IT) injection of MG1-MAGEA3 into tumors and IV pembrolizumab.
In the Phase 1b Expansion for each arm, additional patients will be enrolled at the MTD/MDF as determined in Phase 1 in order to more thoroughly explore immune response, pharmacokinetics/dynamics, and safety for Malignant Melanoma patients who have failed standard therapies.
- Conditions
- Metastatic Melanoma, Squamous Cell Skin Carcinoma
- Being tested
- Ad-MAGEA3, MG1-MAGEA3, Pembrolizumab, Cyclophosphamide
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ad-MAGEA3Drug
Adenovirus vaccine expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen
MG1-MAGEA3Drug
MG1 Maraba oncolytic virus expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen
PembrolizumabDrug
Also called Keytruda
monoclonal antibody; checkpoint inhibitor of PD1
CyclophosphamideDrug
low-dose chemotherapy
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Intravenous Dosing | Experimental | Low dose cyclophosphamide (300mg/ m2) at Day -3, then a fixed dose of Ad-MAGEA3 administered IM on study Day 1. Followed by one of 3 dose levels (escalation) of MG1-MAGEA3 administered as 2 intravenous (IV) doses at Day 15 and Day 18 and fixed dose pembrolizumab (200mg) beginning at either Week 6 or Day 1, depending on the cohort. Receives: Drug: Ad-MAGEA3; Drug: MG1-MAGEA3; Drug: Pembrolizumab; Drug: Cyclophosphamide |
| Arm 2: Intravenous followed by Intratumoral Dosing | Experimental | A fixed dose of Ad-MAGEA3 administered IM followed by Pembrolizumab on Day 1. MG1-MAGEA3 administered as an intravenous (IV) dose at Day 15, followed by intratumoral (IT) MG1-MAGEA3 on Day 22, Day 29, and Day 36. IT MG1-MAGEA3 booster injections may be continued every 3 weeks beginning at Day 43 (Week 6). Receives: Drug: Ad-MAGEA3; Drug: MG1-MAGEA3; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of Ad/MG1-MAGEA3 administration in Melanoma or Squamous Cell Skin Carcinoma
Safety will be determined by assessing the severity and frequency of treatment emergent Adverse Events and clinical laboratory toxicity using NCI CTCAE v 5.0
Measured: 6 months
Determine the maximum tolerated dose (MTD)/ maximum feasible dose (MFD) of Ad/MG1-MAGEA3 in Melanoma or Squamous Cell Skin Carcinoma
MTD/MFD of Ad/MG1-MAGEA3 administered by IV infusion alone and IV infusion followed by direct injection of tumor (IT injection) in Melanoma or Squamous Cell Skin Carcinoma
Measured: 5 weeks
Secondary outcomes (4)
Evaluate Overall Response
Determine the overall response rate (Partial Response (PR) + Complete Response (CR))
Measured: 2 years
Evaluate Disease Control
Determine Disease Control Rate (PR+CR+Stable Disease (SD))
Measured: 2 years
Evaluate PFS
Progression free survival in months
Measured: 2 years
Evaluate Duration of Response, if any
Duration of Response (CR, PR, SD) in months
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2018
- Study start15 Feb 2020
- Primary completion30 Oct 2020 (estimated)
- Study completion31 Dec 2021 (estimated)
Why it stopped: insufficient suitable drug supply
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic MelanomaStudies 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Turnstone Biologics, Corp.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Steve Bernstein, MD, Study director, Turnstone Biologics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03773744
- Sponsor's protocol ID
- Ad/MG1-MAGEA3-003
- Acronym
- Pelican
- Status last verified
- Apr 2021
- First submitted
- 10 Dec 2018
- Last updated
- 6 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Multicenter, Open-label Trial of Oncolytic MG1 Expressing MAGE-A3 (MG1-MAGEA3) With Adenovirus Vaccine Expressing MAGE-A3 (Ad-MAGEA3), in Combination With Immune Modulating Therapy in Patients With Metastatic Melanoma or Previously Treated Cutaneous Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT03773744
- Acronym / sponsor ID
- Pelican / Ad/MG1-MAGEA3-003
- Conditions
- Metastatic Melanoma, Squamous Cell Skin Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: insufficient suitable drug supply
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Turnstone Biologics, Corp.Industry (pharma, biotech, devices)
- Study start
- 15 Feb 2020 (actual)
- Primary completion
- 30 Oct 2020 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 12 Dec 2018 (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.
This is a Phase 1b open-label dose escalation trial of Ad/MG1-MAGEA3 and Pembrolizumab in patients with Metastatic Melanoma or Cutaneous Squamous Cell Skin Cancer that has failed prior standard of care treatments. Upon determination of a Maximum Tolerated Dose (MTD) or Maximum Feasible Dose (MFD) the study will be expanded into up to 24 additional Metastatic Melanoma patients.
Detailed description
This is a Phase 1b open-label dose escalation trial of Ad/MG1-MAGEA3 and Pembrolizumab in patients with Metastatic Melanoma or Cutaneous Squamous Cell Skin Cancer that has failed prior standard of care treatments. This study will consist of two arms where the dose will be increased independently until the maximum tolerated dose (MTD) / maximum feasible dose (MFD) is reached.
Arm 1 - Low-dose cyclophosphamide, followed by an Ad-MAGEA3 intramuscular (IM) prime, followed by intravenous (IV) administration of MG1-MAGEA3 and IV pembrolizumab.
Arm 2 - Ad-MAGEA3 IM injection as a prime, followed by IV administration of MG1-MAGEA3, followed by intratumoral (IT) injection of MG1-MAGEA3 into tumors and IV pembrolizumab.
In the Phase 1b Expansion for each arm, additional patients will be enrolled at the MTD/MDF as determined in Phase 1 in order to more thoroughly explore immune response, pharmacokinetics/dynamics, and safety for Malignant Melanoma patients who have failed standard therapies.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Intravenous Dosing | Experimental | Drug: Ad-MAGEA3, Drug: MG1-MAGEA3, Drug: Pembrolizumab, Drug: CyclophosphamideLow dose cyclophosphamide (300mg/ m2) at Day -3, then a fixed dose of Ad-MAGEA3 administered IM on study Day 1. Followed by one of 3 dose levels (escalation) of MG1-MAGEA3 administered as 2 intravenous (IV) doses at Day 15 and Day 18 and fixed dose pembrolizumab (200mg) beginning at either Week 6 or Day 1, depending on the cohort. |
| Arm 2: Intravenous followed by Intratumoral Dosing | Experimental | Drug: Ad-MAGEA3, Drug: MG1-MAGEA3, Drug: PembrolizumabA fixed dose of Ad-MAGEA3 administered IM followed by Pembrolizumab on Day 1. MG1-MAGEA3 administered as an intravenous (IV) dose at Day 15, followed by intratumoral (IT) MG1-MAGEA3 on Day 22, Day 29, and Day 36. IT MG1-MAGEA3 booster injections may be continued every 3 weeks beginning at Day 43 (Week 6). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Have histologically or cytologically confirmed diagnosis of locally advanced metastatic melanoma or cutaneous squamous cell carcinoma that has failed standard therapies
- For patients treated intratumorally, must have a lesion suitable for direct injection of MG1-MAGEA3
- Have at least one tumor amenable to biopsy
- Have measurable disease via RECIST 1.1 criteria
- Adequate organ function and performance status
Key exclusion criteria (9 listed)
- Prior treatment with any MAGE-A3 vaccine immunotherapy
- Prior systemic therapy for cancer within 4 weeks (8 weeks for lung radiation), and has recovered from chemo-related toxicities to Grade 1 or less
- Intolerant to prior PD1/PD-L1 therapy
- Requires use of anti-platelet or anti-coagulant therapy that cannot be safely suspended for per protocol biopsies or intra-tumoral injections.
- Known active CNS metastases and/or carcinomatous meningitis.
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 |
|---|---|---|
| Ad-MAGEA3Adenovirus vaccine expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen | Drug | Arm 1: Intravenous Dosing, Arm 2: Intravenous followed by Intratumoral Dosing |
| MG1-MAGEA3MG1 Maraba oncolytic virus expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen | Drug | Arm 1: Intravenous Dosing, Arm 2: Intravenous followed by Intratumoral Dosing |
| PembrolizumabAlso: Keytrudamonoclonal antibody; checkpoint inhibitor of PD1 | Drug | Arm 1: Intravenous Dosing, Arm 2: Intravenous followed by Intratumoral Dosing |
| Cyclophosphamidelow-dose chemotherapy | Drug | Arm 1: Intravenous Dosing |
Primary outcome
Safety of Ad/MG1-MAGEA3 administration in Melanoma or Squamous Cell Skin Carcinoma
Time frame: 6 months
Safety will be determined by assessing the severity and frequency of treatment emergent Adverse Events and clinical laboratory toxicity using NCI CTCAE v 5.0
Determine the maximum tolerated dose (MTD)/ maximum feasible dose (MFD) of Ad/MG1-MAGEA3 in Melanoma or Squamous Cell Skin Carcinoma
Time frame: 5 weeks
MTD/MFD of Ad/MG1-MAGEA3 administered by IV infusion alone and IV infusion followed by direct injection of tumor (IT injection) in Melanoma or Squamous Cell Skin Carcinoma
4 secondary outcomes
Evaluate Overall Response
Time frame: 2 years
Evaluate Disease Control
Time frame: 2 years
Evaluate PFS
Time frame: 2 years
Evaluate Duration of Response, if any
Time frame: 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2021.
- 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.
Steve Bernstein, MD study director
Turnstone Biologics
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ad-MAGEA3, MG1-MAGEA3 and Pembrolizumab in people with Metastatic Melanoma and Squamous Cell Skin Carcinoma, run by Turnstone Biologics, Corp..
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 6 inclusion and 9 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: withdrawn, as of the sponsor's last update on 6 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
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 was withdrawn before enrolling participants, so there are no results.
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?
Safety of Ad/MG1-MAGEA3 administration in Melanoma or Squamous Cell Skin Carcinoma (time frame: 6 months). The study lists 2 primary outcomes in all. 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 6 Apr 2021.