Local Progression or Metastatic Melanoma With Failed First-line TreatmentPhase 1/2NCT04849260
Phase Ib/II Clinical Study of Pexa-Vec (Vaccinia GM CSF / Thymidine Kinase-Deactivated Virus) Combined With Recombinant Whole Human Anti-PD-L1 Monoclonal Antibody (ZKAB001) in Metastatic Melanoma
A Phase 1/2 study testing Pexa-Vec combined with ZKAB001 and ZKAB001 monotherapy in people with Local Progression or Metastatic Melanoma With Failed First-line Treatment, run by Lee's Pharmaceutical Limited at 1 site in China.
Trial summary
The study will be divided into two stages: phase Ib and phase II. The safety and phase II recommended dose (RP2D) of Pexa-Vec combined with ZKAB001 in patients with local progression of failed first-line treatment or metastatic melanoma will be evaluated in phase Ib. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Local Progression or Metastatic Melanoma With Failed First-line Treatment
- What is being tested?
- Pexa-Vec combined with ZKAB001 and ZKAB001 monotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteChina
- Study dates
- 26 Aug 2021to 31 May 2023
- Phase
- Phase 1/2
- 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
- Voluntary signing of informed consent.
- Age 18-75 years old (inclusive), regardless of gender.
- Pathologically proved to be malignant melanoma, including skin, mucous membrane, and limb origin, and locally progressive or metastatic melanoma that cannot be completely resected.
- The patient has more than 1 superficial focus for intratumoral injection (suitable for direct or ultrasound-guided injection), which can be skin, subcutaneous or lymph node focus, the longest diameter is (LD) ≥ 1cm and ≤ 10cm, and there is no ulcer in the injected focus.
- Patients who have failed to receive first-line treatment of melanoma in the past, including chemotherapy and targeted therapy.
- Systemic anticancer therapy or adjuvant therapy must be completed at least 4 weeks before enrollment (if previously received nitrosourea or mitomycin C chemotherapy, the interval between the end of chemotherapy and the study group is more than 6 weeks).
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- Patients with adverse events caused by previous treatment recovered to ≤ CTCAE level 1, except for hair loss.
- Measurable lesions based on RECISTv 1.1.
- The ECOG physical condition score is 0 or 1, and the expected survival time is more than 3 months.
- The functions of blood, liver and kidney are good and meet the results of laboratory tests:
- 1) Absolute neutrophil count (ANC) ≥ 1.5x10^9 / L. 2) Platelet ≥ 80 × 10^9 shock L. 3) Hemoglobin ≥ 90g/L. 4) Serum albumin ≥ 28g/L. 5) Bilirubin ≤ 1.5x ULN. 6) ALT and AST ≤ 2.5x ULN, if there is liver metastasis, ALT and AST ≤ 5x ULN. 7) Serum Cr ≤ 1.25 × ULN or endogenous creatinine clearance ≥ 50mL/min (using standard Cockcroft-Gault formula).
- 8) Coagulation function, in which INR ≤1.5 ULN. 9. Female or male patients of childbearing age should take effective contraceptive methods during the study period and within 3 months after the end of the study treatment period. Non-operative sterilization female patients of childbearing age must be negative for serum HCG test during the screening period.
Who cannot join
- Active, known or suspected autoimmune diseases, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granuloma, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis or glomerulonephritis.
- Residual hypothyroidism caused by autoimmune thyroiditis that only requires hormone replacement therapy, controlled type I diabetes, or the absence of external stimulation that is not expected to recur can be included. Patients with eczema, psoriasis, neurodermatitis or vitiligo (patients with psoriatic arthritis will need to be excluded) who only have skin symptoms can be enrolled in the group if they meet the following conditions: the area covered by the rash must be less than 10% of the body surface area; the disease is well controlled at the baseline level, requiring only local steroids, and those with no acute exacerbation in the past 12 months can be included.
- Subjects were treated with immunosuppressants or systemic or absorbable local corticosteroids within 2 weeks before enrollment to achieve immunosuppression (dose > 10mg/ prednisone or equivalent).
- Has received or plans to receive any form of organ transplant, including allogeneic stem cell transplantation.
- Known to be allergic to macromolecular protein preparations, or to any composition of ZKAB001 and Pexa-Vec.
- Severe allergic reactions or side effects occurred in the past vaccination process.
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- Complications of other malignant tumors less than 5 years before the first dose, except for fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical resection, ductal carcinoma in situ after radical resection (hormone therapy for non-metastatic prostate cancer or breast cancer is acceptable)
- Subjects with known active central nervous system (CNS) metastasis and / or carcinomatous meningitis.
- Note: subjects who have previously received brain metastasis treatment and subjects with clinically stable CNS metastasis may be allowed to participate in the study (defined as at least 4 weeks before the first dose of the trial treatment: (1) No new or expanded evidence of CNS metastasis (through MRI); (2) subjects have been treated without hormones for at least 2 weeks; (3) any neurological symptoms have returned to baseline levels.
- Patients with uncontrolled cardiac clinical symptoms or diseases, such as heart failure above NYHA2, unstable angina pectoris, myocardial infarction within 1 year, clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention, left ventricular ejection fraction at rest was less than 50%.
- After injection treatment, tumor swelling and / or necrosis may invade important vascular structures (such as carotid artery) or other important anatomical sites (such as spinal cord).
- A history of severe inflammatory skin diseases requiring drug treatment and a history of severe eczema requiring drug treatment (confirmed by researchers).
- The subjects had active infection, or had a fever of unknown origin during the screening period or within a week before the first administration of the drug > 38.5 ℃. (according to the judgment of the researchers, the fever caused by the tumor can be included in the group.).
- Active hepatitis B or C (unless HBV-DNA titer < 500IU/mL or copy number < 1000copies/ml, HCV-RNA negative can be included in), HIV positive or known history of acquired immunodeficiency syndrome after antiviral treatment.
- Subjects are participating in other clinical studies, or less than one month from the end of the previous clinical study, except for non-interventional clinical studies (such as epidemiological studies).
- HCV therapy could not be stopped within 14 days before Pexa-Vec injection. If a patient is using any antiviral drugs, he or she should consult the researcher to determine whether the patient is suitable to participate in the study.
- Less than 4 weeks from the previous use of immune checkpoint inhibitors, such as PD-1/CTLA-4 inhibitors (that is, more than 4 weeks from the previous receipt of PD-1/CTLA-4 inhibitors); or have been treated with other oncolytic viruses (such as T-Vec, recombinant human GM-CSF herpes simplex virus injection (OrienX010), etc.) or PD-L1 inhibitors.
- The patients were vaccinated with live vaccine within 4 weeks before screening. Inactivated vaccines to prevent influenza and inactivated vaccines to prevent other infectious diseases can be used on a case-by-case basis, but it is necessary to consider increasing the elution period before and after medication.
- Subjects are known to have a history of psychotropic substance abuse, alcohol abuse or drug use.
- Subjects with active pulmonary tuberculosis or with a history of active pulmonary tuberculosis infection within 1 year before medication, with or without treatment.
- The researchers evaluated that there was a significant bleeding event in the previous 12 months and the risk of intratumoral injection procedure increased.
- Pregnant or lactating women.
- The researchers determined that the patient had other factors that might lead to the termination of the study, such as other serious diseases or serious laboratory abnormalities or accompanied by other factors that would affect the safety of the subjects, or family or social factors such as the collection of trial data and samples.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Beijing Cancer Hospital
Beijing
Cui chuanliang, doctor, +861088196348, 1008ccl@163.com
About this study
Official title: Phase Ib/II, Open Label, Controlled Clinical Study of Pexa-Vec (Vaccinia GM CSF / Thymidine Kinase-Deactivated Virus) Combined With Recombinant Whole Human Anti-PD-L1 Monoclonal Antibody (ZKAB001) in Metastatic Melanoma After First-line Treatment Failure
The study will be divided into two stages: phase Ib and phase II. The safety and phase II recommended dose (RP2D) of Pexa-Vec combined with ZKAB001 in patients with local progression of failed first-line treatment or metastatic melanoma will be evaluated in phase Ib.
Objective response rate (ORR) and progression-free survival (PFS) of ZKAB001 combined with RP2D's Pexa-Vec or ZKAB001 monotherapy in patients with local progression or metastatic melanoma will be evaluated in phase II.
Read the detailed description
The study will be divided into two stages: phase Ib and phase II. The safety and phase II recommended dose (RP2D) of Pexa-Vec combined with ZKAB001 in patients with local progression of failed first-line treatment or metastatic melanoma will be evaluated in phase Ib.
Objective response rate (ORR) and progression-free survival (PFS) of ZKAB001 combined with RP2D's Pexa-Vec or ZKAB001 monotherapy in patients with local progression or metastatic melanoma will be evaluated in phase II.
The study is also going to evaluate the combination therapy or monotherapy:
- overall survival time ((OS)), disease control rate (DCR) and duration of remission (DOR) in patients with metastatic melanoma.
- safety
- the relationship between the expression of PD-L1 in tumor tissue and clinical effect；
- the changes of immune microenvironment (CD8+ expression) in tumor tissue before and after Pexa-vec treatment.
- Being tested
- Pexa-Vec combined with ZKAB001, ZKAB001 monotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pexa-Vec combined with ZKAB001Biological
- Intratumoral injection of low dose Pexa-Vec (3×10^8pfu) combined with intravenous of ZKAB001 (5mg/kg), every 2 weeks as one cycle.
- Intratumoral injection of high dose Pexa-Vec (1×10^9pfu) combined with intravenous of ZKAB001 (5mg/kg), every 2 weeks as one cycle.
ZKAB001 monotherapyBiological
ZKAB001 monotherapy
| Study group | Role | What they receive |
|---|---|---|
| Pexa-Vec combined with ZKAB001 | Experimental | The combined treatment group is divided into two dose groups. The principle of "3+3" is adopted to determine RP2D, and RP2D will be used in subsequent patients in this cohort. Receives: Biological: Pexa-Vec combined with ZKAB001 |
| ZKAB001 monotherapy | Active comparator | ZKAB001 monotherapy. Receives: Biological: ZKAB001 monotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
dose-limited toxicity (DLT)
dose-limited toxicity (DLT)
Measured: 28 days after first dose
maximum tolerated dose (MTD)
recommended phase 2 dose RP2D.
Measured: 28 days after first dose
progression free survival (PFS)
progression free survival
Measured: 2 years
objective response rate
objective response rate
Measured: 2 years
Secondary outcomes (5)
disease control rate (DCR)
disease control rate
Measured: 2 years
duration of response (DOR)
duration of response
Measured: 2 years
6-month and 1-year PFS rate
6-month and 1-year PFS rate
Measured: 12 months
1-year and 2-year OS rates
1-year and 2-year OS rates
Measured: 2 years
AE/SAEs
The incidence and severity of adverse events (AE) and severe adverse events (SAE).
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 posted19 Apr 2021
- Study start26 Aug 2021
- Primary completion31 May 2022 (estimated)
- Study completion31 May 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Local Progression or Metastatic Melanoma With Failed First-line TreatmentStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Lee's Pharmaceutical Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04849260
- Sponsor's protocol ID
- ZKAB001-LEES-2019-02
- Status last verified
- Mar 2022
- First submitted
- 14 Apr 2021
- Last updated
- 31 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib/II, Open Label, Controlled Clinical Study of Pexa-Vec (Vaccinia GM CSF / Thymidine Kinase-Deactivated Virus) Combined With Recombinant Whole Human Anti-PD-L1 Monoclonal Antibody (ZKAB001) in Metastatic Melanoma After First-line Treatment Failure
- ClinicalTrials.gov ID
- NCT04849260
- Acronym / sponsor ID
- ZKAB001-LEES-2019-02
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Lee's Pharmaceutical LimitedIndustry (pharma, biotech, devices)
- Study start
- 26 Aug 2021 (actual)
- Primary completion
- 31 May 2022 (estimated)
- Study completion
- 31 May 2023 (estimated)
- First posted
- 19 Apr 2021 (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.
The study will be divided into two stages: phase Ib and phase II. The safety and phase II recommended dose (RP2D) of Pexa-Vec combined with ZKAB001 in patients with local progression of failed first-line treatment or metastatic melanoma will be evaluated in phase Ib.
Objective response rate (ORR) and progression-free survival (PFS) of ZKAB001 combined with RP2D's Pexa-Vec or ZKAB001 monotherapy in patients with local progression or metastatic melanoma will be evaluated in phase II.
Detailed description
The study will be divided into two stages: phase Ib and phase II. The safety and phase II recommended dose (RP2D) of Pexa-Vec combined with ZKAB001 in patients with local progression of failed first-line treatment or metastatic melanoma will be evaluated in phase Ib.
Objective response rate (ORR) and progression-free survival (PFS) of ZKAB001 combined with RP2D's Pexa-Vec or ZKAB001 monotherapy in patients with local progression or metastatic melanoma will be evaluated in phase II.
The study is also going to evaluate the combination therapy or monotherapy:
- overall survival time ((OS)), disease control rate (DCR) and duration of remission (DOR) in patients with metastatic melanoma.
- safety
- the relationship between the expression of PD-L1 in tumor tissue and clinical effect；
- the changes of immune microenvironment (CD8+ expression) in tumor tissue before and after Pexa-vec treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pexa-Vec combined with ZKAB001 | Experimental | Biological: Pexa-Vec combined with ZKAB001The combined treatment group is divided into two dose groups. The principle of "3+3" is adopted to determine RP2D, and RP2D will be used in subsequent patients in this cohort. |
| ZKAB001 monotherapy | Active comparator | Biological: ZKAB001 monotherapyZKAB001 monotherapy. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Voluntary signing of informed consent.
- Age 18-75 years old (inclusive), regardless of gender.
- Pathologically proved to be malignant melanoma, including skin, mucous membrane, and limb origin, and locally progressive or metastatic melanoma that cannot be completely resected.
- The patient has more than 1 superficial focus for intratumoral injection (suitable for direct or ultrasound-guided injection), which can be skin, subcutaneous or lymph node focus, the longest diameter is (LD) ≥ 1cm and ≤ 10cm, and there is no ulcer in the injected focus.
- Patients who have failed to receive first-line treatment of melanoma in the past, including chemotherapy and targeted therapy.
Key exclusion criteria (23 listed)
- Active, known or suspected autoimmune diseases, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granuloma, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis or glomerulonephritis.
- Residual hypothyroidism caused by autoimmune thyroiditis that only requires hormone replacement therapy, controlled type I diabetes, or the absence of external stimulation that is not expected to recur can be included. Patients with eczema, psoriasis, neurodermatitis or vitiligo (patients with psoriatic arthritis will need to be excluded) who only have skin symptoms can be enrolled in the group if they meet the following conditions: the area covered by the rash must be less than 10% of the body surface area; the disease is well controlled at the baseline level, requiring only local steroids, and those with no acute exacerbation in the past 12 months can be included.
- Subjects were treated with immunosuppressants or systemic or absorbable local corticosteroids within 2 weeks before enrollment to achieve immunosuppression (dose > 10mg/ prednisone or equivalent).
- Has received or plans to receive any form of organ transplant, including allogeneic stem cell transplantation.
- Known to be allergic to macromolecular protein preparations, or to any composition of ZKAB001 and Pexa-Vec.
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 |
|---|---|---|
| Pexa-Vec combined with ZKAB0011. Intratumoral injection of low dose Pexa-Vec (3×10^8pfu) combined with intravenous of ZKAB001 (5mg/kg), every 2 weeks as one cycle. 2. Intratumoral injection of high dose Pexa-Vec (1×10^9pfu) combined with intravenous of ZKAB001 (5mg/kg), every 2 weeks as one cycle. | Biological | Pexa-Vec combined with ZKAB001 |
| ZKAB001 monotherapyZKAB001 monotherapy | Biological | ZKAB001 monotherapy |
Primary outcome
dose-limited toxicity (DLT)
Time frame: 28 days after first dose
dose-limited toxicity (DLT)
maximum tolerated dose (MTD)
Time frame: 28 days after first dose
recommended phase 2 dose RP2D.
progression free survival (PFS)
Time frame: 2 years
progression free survival
objective response rate
Time frame: 2 years
objective response rate
5 secondary outcomes
disease control rate (DCR)
Time frame: 2 years
duration of response (DOR)
Time frame: 2 years
6-month and 1-year PFS rate
Time frame: 12 months
1-year and 2-year OS rates
Time frame: 2 years
AE/SAEs
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2022.
- Individual participant dataSharing planned: No
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pexa-Vec combined with ZKAB001 and ZKAB001 monotherapy in people with Local Progression or Metastatic Melanoma With Failed First-line Treatment, run by Lee's Pharmaceutical Limited 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 12 inclusion and 23 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 31 Mar 2022. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Cui chuanliang, doctor (+86 010 88196348, 1008ccl@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
dose-limited toxicity (DLT) (time frame: 28 days after first dose). 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?
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 31 Mar 2022.