Melanoma (Skin)Phase 1NCT04072900
A Personalized NeoAntigen Cancer Vaccine Combined With Anti-PD-1 in Melanoma
A Phase 1 study testing Peptide, Anti-PD-1 and rhGM-CSF in people with Melanoma (Skin), run by Xiangya Hospital of Central South University at 1 site in China.
Trial summary
This study assessed the safety and efficacy of individualized new antigen cancer vaccine combined with Programmed Cell Death Protein 1（PD1） inhibitor Toripalimab in the treatment of metastatic cutaneous melanoma. Melanoma is the most malignant skin neoplasm. Immunotherapy is the main treatment at present. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Melanoma (Skin)
- What is being tested?
- Peptide, Anti-PD-1 and rhGM-CSF
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 21 Apr 2020to 1 Sep 2022
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must meet the following criteria on screening examination to be eligible to participate in the study:
- Patient is willing and able to give written informed consent.
- Age ≥ 18 years, ≤75 years
- Pathologically confirmed, clinically evident (by physical examination or radiographic imaging) stage IIIDN3c、IVM1a、M1b、M1c cutaneous melanoma.
- Lesions that can be measured，and at least one lesion that can be used to evaluate the efficacy of immunotherapy;Multiple biopsies are available for lesions.
- Patient is agreeable to allow tumor、normal tissue samples and blood samples to be submitted for genomic/complete exome/transcriptional sequencing；
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- ECOG score is 0 or 1
- Life expectancy >6 months
- Normal organ and bone marrow function as defined below:
- Leukocytes ≥ 3,500/mcL Absolute lymphocyte count > 800/mcL Absolute neutrophil count > 1,500/mcL Platelets > 100,000/mcL Hemoglobin > 10.0 g/dL Total serum bilirubin < 1.0 x institutional upper limit of normal AST (SGOT)/ALT (SGPT) < 2.0 x institutional upper limit of normal Serum creatinine< 1.5 x institutional upper limit of normal
- Women of childbearing potential (WOCBP) must have a negative pregnancy test before entering the trial and within 7 days prior to start of study medication.
- Female patients enrolled in the study, short-term have no fertility plan and must agree to use an adequate method of contraception starting with the first dose of study therapy through 90 days after the last dose of study therapy.
- Male patients must agree to use an adequate method of contraception starting with the first dose of study therapy through 90 days after the last dose of study therapy.
- Good compliance, able to follow research protocols and follow-up procedures.
Who cannot join
- Patients who meet any of the following criteria will not be eligible for this study.
- Uveal or mucosal melanoma；
- Patients who received immunotherapy or other targeted cancer therapy within 4 weeks (including, but not limited to: IL-2, CTLA-4 blockade, PD-1/PD-L1 blockade, but exception of INF-α given as adjuvant treatment)
- Previous bone marrow or stem cell transplant
- History of severe allergic reactions attributed to any vaccine therapy
- Active, known, or suspected autoimmune disease with the exception of vitiligo, type 1 diabetes, or psoriasis not requiring systemic treatment.
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- Use of a non-oncology vaccine therapy for prevention of infectious diseases (up-to) 4 weeks prior to enrollment to the study. Patients may not receive any non-oncology vaccine therapy during the period of NeoVax administration and until at least 8 weeks after the last dose of study therapy
- In an immunosuppressive stage or immunosuppressive drugs were used systematically within 2 weeks.
- Patients with long-term use of glucocorticoids or with experimental anti-tumor drugs
- Active bacterial or fungal infections identified clinically (>= level 2 of NCI-CTC edition 3);
- Known chronic infections with HIV, hepatitis B or C
- Known active or latent tuberculosis infection
- A history of idiopathic pulmonary fibrosis and organized pneumonia, or active pneumonia on chest computed tomography.
- Complicated with other tumors, except for cervical cancer in situ and basal cell carcinoma five years ago.
- Severe coronary or cerebrovascular disease, or other diseases that the investigators considered should to be exclusion;
- Drug abuse, Clinical, psychological or social factor result in affecting informed consent or research implementation.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Xiangya Hospital, Central South University
Changsha, Hunan, 410008
Juan Su, +86-8432-7128, sujuanderm@csu.edu.cn
Xiang Chen, +86-8975-3406, chenxiangck@126.com
About this study
Official title: A Phase I Study With a Personalized NeoAntigen Cancer Vaccine Combined With Anti-PD-1 in Metastatic Melanoma
This study assessed the safety and efficacy of individualized new antigen cancer vaccine combined with Programmed Cell Death Protein 1（PD1） inhibitor Toripalimab in the treatment of metastatic cutaneous melanoma. Melanoma is the most malignant skin neoplasm. Immunotherapy is the main treatment at present. PD1 is an immunological checkpoint and the inhibitors can reduce the immune escape of tumors, enhance T cell function and kill tumors. At present, PD1 antibody is the representative drug of immunotherapy, but the overall efficiency of its single drug treatment of acral melanoma is still low, and the combined treatment can significantly improve the efficiency. Melanoma has a high mutation load, which makes each patient have mutations specific to individual patients and tumors (changes in genetic material). These mutations lead to tumour cells producing proteins that are distinct from those of the body's own cells. These proteins used in vaccines may cause a strong immune response, which may help participants' bodies fight against any cancer cells that may lead to future recurrence of melanoma. Inhibition of PD1 can enhance the activity of T cells and form T cells with sustained killing activity. Tumor vaccines activate human Antigen Presenting Cells (APC) by injecting tumor antigens and adjuvants, and then activate T cells by APC to produce specific killing T cells. Therefore, the combination of "tumor vaccine + PD1 inhibitor" can produce effective specific killing and sustained activation of T cells, and prevent the establishment of inhibitory tumor microenvironment by tumor cells. The study will examine the safety and efficiency of the combined therapy at different time points and assess whether there is an immune response in the patient's peripheral blood and tumor tissue.
- Conditions
- Melanoma (Skin)
- Being tested
- Peptide, Anti-PD-1, rhGM-CSF, Imiquimod 5% Topical Cream
- Keywords
- Melanoma, Metastasis
- Medical subject headings
- Melanoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PeptideDrug
Also called NeoAntigen peptides
4 x 3 mg all the peptides given on days 84，87，91，98，105，133，and 161
Anti-PD-1Drug
Also called Toripalimab
3mg/kg, ivgtt, Q2w
rhGM-CSFDrug
3μg/kg given on Days 81，82，83，95，96，97，102，103，104，130，131，132，158，159，and 160
Imiquimod 5% Topical CreamDrug
topical application on the injection site 6 hours before each NeoAntigen peptides injection
| Study group | Role | What they receive |
|---|---|---|
| Intervention/Treatment | Experimental | Personalized NeoAntigen Cancer Vaccine- Neo-Vac-Mn (peptides + rhGM-CSF+anti-PD1+Imiquimod 5% Topical Cream)
NeoAntigen peptides:4 x 2 mg the total peptides given on days 84，87，91，98，105，133，and 161
Anti-PD-1 Toripalimab: 3mg/kg, ivgtt, Q2w
rhGM-CSF: 3μg/kg given on Days 81，82，83，95，96，97，102，103，104，130，131，132，158，159，and 160
Imiquimod 5% Topical Cream:topical application on the injection site 6 hours before each NeoAntigen peptides injection Receives: Drug: Peptide; Drug: Anti-PD-1; Drug: rhGM-CSF; Drug: Imiquimod 5% Topical Cream |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants experiencing adverse events
Number of participants experiencing clinical and laboratory adverse events (AE)
Measured: up to a maximum of 252 days
Number of Patients with Complete Remission Rate
Number of Patients with Complete Remission Rate（CRR）
Measured: up to a maximum of 252 days
Number of Patients with Progressive Disease
Number of Patients with Progressive Disease（PD）
Measured: up to a maximum of 252 days
Number of Patients with Partial Response
Number of Patients with Partial Response（PR）
Measured: up to a maximum of 252 days
Secondary outcomes (1)
Monitoring of cellular immune response
the immune response of serum and tumor tissue
Measured: up to a maximum of 252 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2019
- Study start21 Apr 2020 (estimated)
- Primary completion1 Sep 2021 (estimated)
- Study completion1 Sep 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Melanoma (Skin)Studies of the same condition, open and under way.
- More trials run by Xiangya Hospital of Central South UniversityThe sponsor's other registered studies.
- 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
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xiangya Hospital of Central South University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, pfkchenxiang, Xiangya Hospital of Central South University
- Investigators
- Xiang Chen, Doctor's, Principal investigator, Xiangya Hospital of Central South University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04072900
- Sponsor's protocol ID
- XYM001
- Status last verified
- Apr 2020
- First submitted
- 26 Jul 2019
- Last updated
- 28 Apr 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Ott PA, Hu Z, Keskin DB, Shukla SA, Sun J, Bozym DJ, Zhang W, Luoma A, Giobbie-Hurder A, Peter L, Chen C, Olive O, Carter TA, Li S, Lieb DJ, Eisenhaure T, Gjini E, Stevens J, Lane WJ, Javeri I, Nellaiappan K, Salazar AM, Daley H, Seaman M, Buchbinder EI, Yoon CH, Harden M, Lennon N, Gabriel S, Rodig SJ, Barouch DH, Aster JC, Getz G, Wucherpfennig K, Neuberg D, Ritz J, Lander ES, Fritsch EF, Hacohen N, Wu CJ. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. 2017 Jul 13;547(7662):217-221. doi: 10.1038/nature22991. Epub 2017 Jul 5.
PubMed 28678778Sahin U, Derhovanessian E, Miller M, Kloke BP, Simon P, Lower M, Bukur V, Tadmor AD, Luxemburger U, Schrors B, Omokoko T, Vormehr M, Albrecht C, Paruzynski A, Kuhn AN, Buck J, Heesch S, Schreeb KH, Muller F, Ortseifer I, Vogler I, Godehardt E, Attig S, Rae R, Breitkreuz A, Tolliver C, Suchan M, Martic G, Hohberger A, Sorn P, Diekmann J, Ciesla J, Waksmann O, Bruck AK, Witt M, Zillgen M, Rothermel A, Kasemann B, Langer D, Bolte S, Diken M, Kreiter S, Nemecek R, Gebhardt C, Grabbe S, Holler C, Utikal J, Huber C, Loquai C, Tureci O. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature. 2017 Jul 13;547(7662):222-226. doi: 10.1038/nature23003. Epub 2017 Jul 5.
PubMed 28678784
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study With a Personalized NeoAntigen Cancer Vaccine Combined With Anti-PD-1 in Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT04072900
- Acronym / sponsor ID
- XYM001
- Conditions
- Melanoma (Skin)
- Keywords
- Melanoma, Metastasis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Xiangya Hospital of Central South UniversityUniversity, hospital or other
- Study start
- 21 Apr 2020 (estimated)
- Primary completion
- 1 Sep 2021 (estimated)
- Study completion
- 1 Sep 2022 (estimated)
- First posted
- 28 Aug 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.
This study assessed the safety and efficacy of individualized new antigen cancer vaccine combined with Programmed Cell Death Protein 1（PD1） inhibitor Toripalimab in the treatment of metastatic cutaneous melanoma. Melanoma is the most malignant skin neoplasm. Immunotherapy is the main treatment at present. PD1 is an immunological checkpoint and the inhibitors can reduce the immune escape of tumors, enhance T cell function and kill tumors. At present, PD1 antibody is the representative drug of immunotherapy, but the overall efficiency of its single drug treatment of acral melanoma is still low, and the combined treatment can significantly improve the efficiency. Melanoma has a high mutation load, which makes each patient have mutations specific to individual patients and tumors (changes in genetic material). These mutations lead to tumour cells producing proteins that are distinct from those of the body's own cells. These proteins used in vaccines may cause a strong immune response, which may help participants' bodies fight against any cancer cells that may lead to future recurrence of melanoma. Inhibition of PD1 can enhance the activity of T cells and form T cells with sustained killing activity. Tumor vaccines activate human Antigen Presenting Cells (APC) by injecting tumor antigens and adjuvants, and then activate T cells by APC to produce specific killing T cells. Therefore, the combination of "tumor vaccine + PD1 inhibitor" can produce effective specific killing and sustained activation of T cells, and prevent the establishment of inhibitory tumor microenvironment by tumor cells. The study will examine the safety and efficiency of the combined therapy at different time points and assess whether there is an immune response in the patient's peripheral blood and tumor tissue.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention/Treatment | Experimental | Drug: Peptide, Drug: Anti-PD-1, Drug: rhGM-CSF, Drug: Imiquimod 5% Topical CreamPersonalized NeoAntigen Cancer Vaccine- Neo-Vac-Mn (peptides + rhGM-CSF+anti-PD1+Imiquimod 5% Topical Cream) NeoAntigen peptides:4 x 2 mg the total peptides given on days 84，87，91，98，105，133，and 161 Anti-PD-1 Toripalimab: 3mg/kg, ivgtt, Q2w rhGM-CSF: 3μg/kg given on Days 81，82，83，95，96，97，102，103，104，130，131，132，158，159，and 160 Imiquimod 5% Topical Cream:topical application on the injection site 6 hours before each NeoAntigen peptides injection |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients must meet the following criteria on screening examination to be eligible to participate in the study:
- Patient is willing and able to give written informed consent.
- Age ≥ 18 years, ≤75 years
- Pathologically confirmed, clinically evident (by physical examination or radiographic imaging) stage IIIDN3c、IVM1a、M1b、M1c cutaneous melanoma.
- Lesions that can be measured，and at least one lesion that can be used to evaluate the efficacy of immunotherapy;Multiple biopsies are available for lesions.
Key exclusion criteria (16 listed)
- Patients who meet any of the following criteria will not be eligible for this study.
- Uveal or mucosal melanoma；
- Patients who received immunotherapy or other targeted cancer therapy within 4 weeks (including, but not limited to: IL-2, CTLA-4 blockade, PD-1/PD-L1 blockade, but exception of INF-α given as adjuvant treatment)
- Previous bone marrow or stem cell transplant
- History of severe allergic reactions attributed to any vaccine therapy
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 |
|---|---|---|
| PeptideAlso: NeoAntigen peptides4 x 3 mg all the peptides given on days 84，87，91，98，105，133，and 161 | Drug | Intervention/Treatment |
| Anti-PD-1Also: Toripalimab3mg/kg, ivgtt, Q2w | Drug | Intervention/Treatment |
| rhGM-CSF3μg/kg given on Days 81，82，83，95，96，97，102，103，104，130，131，132，158，159，and 160 | Drug | Intervention/Treatment |
| Imiquimod 5% Topical Creamtopical application on the injection site 6 hours before each NeoAntigen peptides injection | Drug | Intervention/Treatment |
Primary outcome
Number of participants experiencing adverse events
Time frame: up to a maximum of 252 days
Number of participants experiencing clinical and laboratory adverse events (AE)
Number of Patients with Complete Remission Rate
Time frame: up to a maximum of 252 days
Number of Patients with Complete Remission Rate（CRR）
Number of Patients with Progressive Disease
Time frame: up to a maximum of 252 days
Number of Patients with Progressive Disease（PD）
Number of Patients with Partial Response
Time frame: up to a maximum of 252 days
Number of Patients with Partial Response（PR）
1 secondary outcome
Monitoring of cellular immune response
Time frame: up to a maximum of 252 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2020.
- Results publication: PubMed 28678778Ott PA, Hu Z, Keskin DB, Shukla SA, Sun J, Bozym DJ, Zhang W, Luoma A, Giobbie-Hurder A, Peter L, Chen C, Olive O, Carter TA, Li S, Lieb DJ, Eisenhaure T, Gjini E, Stevens J, Lane WJ, Javeri I, Nellaiappan K, Salazar AM, Daley H, Seaman M, Buchbinder EI, Yoon CH, Harden M, Lennon N, Gabriel S, Rodig SJ, Barouch DH, Aster JC, Getz G, Wucherpfennig K, Neuberg D, Ritz J, Lander ES, Fritsch EF, Hacohen N, Wu CJ. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature. 2017 Jul 13;547(7662):217-221. doi: 10.1038/nature22991. Epub 2017 Jul 5.
- Results publication: PubMed 28678784Sahin U, Derhovanessian E, Miller M, Kloke BP, Simon P, Lower M, Bukur V, Tadmor AD, Luxemburger U, Schrors B, Omokoko T, Vormehr M, Albrecht C, Paruzynski A, Kuhn AN, Buck J, Heesch S, Schreeb KH, Muller F, Ortseifer I, Vogler I, Godehardt E, Attig S, Rae R, Breitkreuz A, Tolliver C, Suchan M, Martic G, Hohberger A, Sorn P, Diekmann J, Ciesla J, Waksmann O, Bruck AK, Witt M, Zillgen M, Rothermel A, Kasemann B, Langer D, Bolte S, Diken M, Kreiter S, Nemecek R, Gebhardt C, Grabbe S, Holler C, Utikal J, Huber C, Loquai C, Tureci O. Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer. Nature. 2017 Jul 13;547(7662):222-226. doi: 10.1038/nature23003. Epub 2017 Jul 5.
- Individual participant dataSharing planned: Undecided
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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.
Xiang Chen, Doctor's principal investigator
Xiangya Hospital of Central South University
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 Peptide, Anti-PD-1 and rhGM-CSF in people with Melanoma (Skin), run by Xiangya Hospital of Central South University at 1 site in China.
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 14 inclusion and 16 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: status not confirmed, as of the sponsor's last update on 28 Apr 2020. 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 China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xiang Chen, Doctor's (+86-8975-3406, chenxiangck@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants experiencing adverse events (time frame: up to a maximum of 252 days). The study lists 4 primary outcomes in all. 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 NCT04072900, 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 28 Apr 2020.