MelanomaPhase 1NCT04756934
A Study of HX008 Plus LP002 for the Treatment of Patients With Advanced Melanoma
A Phase 1 study testing HX008 and LP002 in people with Melanoma, run by Taizhou HoudeAoke Biomedical Co., Ltd. at 1 site in China.
Trial summary
The subsequent treatment choices for the patients with advanced melanoma, who have failed the immune checkpoint inhibitor therapy of single agent. Evidences showed that PD-1 and PD-L1 signalling pathways are not redundant. Blocking both of them could produce synergistic effect. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Melanoma
- What is being tested?
- HX008 and LP002
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 1 siteChina
- Study dates
- 20 Aug 2020to 20 Aug 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
- Provide written informed consent voluntarily. Understand this protocol and be willing and able to adhere to the study visit schedule.
- Male and Female aged 18 to 75 are eligible.
- Histologic diagnosis of locally advanced or metastatic melanoma, who are unable to undergo complete resection, while ocular melanoma is excluded, and the overall rate of mucosal melanoma is no more than 22%.
- Has experienced progressed disease in previous anti-PD-1 or PD-L1 therapy for the locally advanced or metastatic melanoma (anti-PD-1 or PD-L1 therapy as neo-adjuvant or adjuvant therapy could be accepted if progressed disease occured with 6 months after the last dose of treatment).
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
- Life expectancy ≥ 3 months.
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- With at least 1 measurable extracranial lesion based on RECIST v1.1, and no previous radiotherapy administrated to the measurable lesions.
- Central nervous system metastases must be asymptomatic with or without treatment, and be stable for at least 3 months based on CT/MRI, and no need for systemic steroids within 4 weeks prior to the first dose of the study drug.
- Provide with tumor specimen (for testing the expression of PD -L1).
- Has sufficient organ and bone marrow function to meet the following laboratory examination standards (without blood transfusion within 14 days prior to enrollment): neutrophils ≥ 1.5 x 10^9/L; white blood cells ≥3.0 x 10^9/L; platelets ≥ 100 x 10^9/L; hemoglobin ≥ 90 g/L; serum creatinine ≤1.5x ULN; aspartic transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis; total bilirubin ≤ 1.5 x ULN; INR≤2 x ULN, aPTT≤1.5 x ULN (except for those undergoing anticoagulant therapy).
- Reproductive men and women of childbearing age are willing to take effective contraceptive measures from signing the informed consent form to 3 months after the last administration of the trial drug.
Who cannot join
- Prior malignancy active within the previous 5 years except for locally curable cancers that have been apparently cured, such as carcinoma in situ of the cervix or basal cell skin cancer.
- Has experienced severe immunotherapy related toxicity in the previous anti-PD-1 / PD-L1 monoclonal antibody treatment, including but not limited to: Grade 3 / 4 pneumonia, proteinuria, uveitis or upper scleritis, myasthenia gravis, pancreatitis, hepatitis, bullous skin diseases (including SJS, TEN); grade 2-4 encephalitis, myocarditis; any grade of Guillain Barre syndrome, transverse myelitis; severe inflammatory arthritis that significantly impact the quality of patient's life;
- Known to has BRAF V600 mutation before signing informed consent form, and has not received any corresponding targeted therapy.
- With adverse reactions of previous treatment that have not recovered to CTCAE V5.0 grade ≤ 1, except for the residual hair loss effect.
- With active or history of autoimmune diseases that may recur (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulitis, etc.), or patients with high risk (e.g., organ transplantation requiring immunosuppressive therapy). While those with the following diseases were allowed to be enrolled: a) Stable patients with type I diabetes after a fixed dose of insulin; b) Autoimmune hypothyroidism requiring hormone replacement therapy only; c) Skin diseases requiring no systemic treatment (e.g. eczema, skin rash covering less than 10% of the body surface, psoriasis without ophthalmic symptoms, etc.).
- Expecting to receive major surgery during the study period including 4 weeks prior to the first dose of the study drug.
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- Need to receive systemic corticosteroids (dose equivalent to > 10 mg prednisone / day) or other immunosuppressive drugs within 14 days before enrollment or during the study period. Those under the following conditions are eligible: a) Locally external use or inhaled corticosteroids; b) short-term (≤ 7 days) use of glucocorticoids for the prevention or treatment of non autoimmune allergic diseases.
- Has active digestive ulcer, incomplete intestinal obstruction, active gastrointestinal hemorrhage or perforation.
- Has active interstitial pneumonia, pulmonary fibrosis, acute pulmonary disorders, et al.
- Has uncontrolled systemic diseases, for instance, cardiovascular and cerebrovascular disease, diabetes, hypertension, tuberculosis.
- History of human immunodeficiency virus infection, acquired or congenital immunodeficiency disease, organ transplantation or stem cell transplantation.
- Has active chronic HBV or HCV infection, except those with HBV DNA viral load ≤500 IU/mL or <10^3 copies/mL, or HCV RNA negative after adequate treatment.
- Has severe infection within 4 weeks or active infection requiring IV infusion or oral administration of antibiotics within 2 weeks prior to the first dose of the study drug.
- Known to be allergic to macromolecular protein agents or monoclonal antibody; Known to has a history of severe allergies (CTCAE v5.0 ≥ grade 3) to any of the components in the study drug.
- Has participated in other clinical trial within 4 weeks prior to the first dose of the study drug.
- Alcohol dependence or drug abuse within recent one year.
- Has a history of confirmed neurological or mental disorders, such as epilepsy, dementia; or with poor compliance; or the presence of peripheral neurological disorders.
- Is pregnant or breastfeeding.
- Has received a live vaccine within 30 days prior to the first dose of trial treatment.
- Other reasons disqualifying the entering of this study based on the evaluation of the investigators.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Beijing Cancer Hospital
Beijing, Beijing Municipality, 100142
Jun Guo, MD, 010-88140650, guoj307@126.com
About this study
Official title: A Phase I Study of Tolerance and Pharmacokinetics of HX008 (a Humanized Monoclonal Antibody Targeting PD-1) Plus LP002 (a Humanized Monoclonal Antibody Targeting PD-L1) in Patients With Locally Advanced or Metastatic Melanoma Who Have Experienced Progressed Disease in Previous Anti-PD-1 or PD-L1 Therapy.
The subsequent treatment choices for the patients with advanced melanoma, who have failed the immune checkpoint inhibitor therapy of single agent. Evidences showed that PD-1 and PD-L1 signalling pathways are not redundant. Blocking both of them could produce synergistic effect. HX008 and LP002 are humanized monoclonal antibodies targeting PD-1 on T cells and PD-L1 on tumor cells respectively. In this study, participants with locally advanced or metastatic melanoma who have failed previous anti-PD-1 or PD-L1 will be administrated with HX008 plus LP002. The safety and preliminary efficacy will be evaluated.
- Conditions
- Melanoma
- Being tested
- HX008, LP002
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HX008Drug
HX008: 200mg, Q3W
LP002Drug
LP002: 1mg/kg, or 3mg/kg, or 5mg/kg, Q3W
| Study group | Role | What they receive |
|---|---|---|
| Ia: LP002 dose escalation-1mg/kg | Experimental | 3-6 participants will receive HX008 of 200mg, Q3W plus LP002 of 1mg/kg, Q3W for up to 1 year. Receives: Drug: HX008; Drug: LP002 |
| Ia: LP002 dose escalation-3mg/kg | Experimental | 3-6 participants will receive HX008 of 200mg, Q3W plus LP002 of 3mg/kg, Q3W for up to 1 year. Receives: Drug: HX008; Drug: LP002 |
| Ia: LP002 dose escalation-5mg/kg | Experimental | 3-6 participants will receive HX008 of 200mg, Q3W plus LP002 of 5mg/kg, Q3W for up to 1 year. Receives: Drug: HX008; Drug: LP002 |
| Ib: Expansion | Experimental | Approximately 30 participants will receive HX008 of 200mg, Q3W plus LP002 of the recommended dose, Q3W for up to 1 year. Receives: Drug: HX008; Drug: LP002 |
| Ib: Control | Experimental | Approximately 15 participants will receive LP002 of recommended dose, Q3W for up to 1 year. Receives: Drug: LP002 |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT (dose limited toxicity) rate
To observe how many participants experience DLT in each LP002 dose group in phase Ia.
Measured: 6 months
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Measured: 2 years
Objective Response Rate (ORR)
Percentage of subjects achieving complete response (CR) and partial response (PR).
Measured: 1 year
Terminal half-life (T1 / 2) of HX008 and LP002
Measured: 1 year
Area under curve (AUC) of HX008 and LP002
Measured: 1 year
Apparent volume of distribution of HX008 and LP002
Measured: 1 year
Systemic clearance of HX008 and LP002
Measured: 1 year
Cmax of HX008 and LP002
Measured: 1 year
Cmin of HX008 and LP002
Measured: 1 year
Tmax of HX008 and LP002
Measured: 1 year
Secondary outcomes (4)
Disease Control Rate (DCR)
Disease Control Rate (DCR) refers to the proportion of subjects who achieve CR, PR and SD through imaging evaluation.
Measured: 1 year
Duration of Response (DOR)
Duration of Response (DOR) is defined as the time from the first evidence of response (PR or CR) to the first evidence of PD or the date of death for any reason.
Measured: 2 years
Progression-Free Survival (PFS)
Progression-free survival (PFS) is defined as the time from the first study drug treatment to disease progression (PD) or to death of the subject due to any reason.
Measured: 2 years
Overall survival (OS)
Overall survival (OS) refers to the time from the first study drug treatment to death due to any cause.
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 posted16 Feb 2021
- Study start20 Aug 2020
- Primary completion20 Aug 2021 (estimated)
- Study completion20 Aug 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 63 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Taizhou HoudeAoke Biomedical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04756934
- Sponsor's protocol ID
- LP002-LH001
- Status last verified
- Feb 2021
- First submitted
- 8 Feb 2021
- Last updated
- 16 Feb 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Tolerance and Pharmacokinetics of HX008 (a Humanized Monoclonal Antibody Targeting PD-1) Plus LP002 (a Humanized Monoclonal Antibody Targeting PD-L1) in Patients With Locally Advanced or Metastatic Melanoma Who Have Experienced Progressed Disease in Previous Anti-PD-1 or PD-L1 Therapy.
- ClinicalTrials.gov ID
- NCT04756934
- Acronym / sponsor ID
- LP002-LH001
- Conditions
- Melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 63 participants (estimated)
- Lead sponsor
- Taizhou HoudeAoke Biomedical Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 20 Aug 2020 (actual)
- Primary completion
- 20 Aug 2021 (estimated)
- Study completion
- 20 Aug 2022 (estimated)
- First posted
- 16 Feb 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 subsequent treatment choices for the patients with advanced melanoma, who have failed the immune checkpoint inhibitor therapy of single agent. Evidences showed that PD-1 and PD-L1 signalling pathways are not redundant. Blocking both of them could produce synergistic effect. HX008 and LP002 are humanized monoclonal antibodies targeting PD-1 on T cells and PD-L1 on tumor cells respectively. In this study, participants with locally advanced or metastatic melanoma who have failed previous anti-PD-1 or PD-L1 will be administrated with HX008 plus LP002. The safety and preliminary efficacy will be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Ia: LP002 dose escalation-1mg/kg | Experimental | Drug: HX008, Drug: LP0023-6 participants will receive HX008 of 200mg, Q3W plus LP002 of 1mg/kg, Q3W for up to 1 year. |
| Ia: LP002 dose escalation-3mg/kg | Experimental | Drug: HX008, Drug: LP0023-6 participants will receive HX008 of 200mg, Q3W plus LP002 of 3mg/kg, Q3W for up to 1 year. |
| Ia: LP002 dose escalation-5mg/kg | Experimental | Drug: HX008, Drug: LP0023-6 participants will receive HX008 of 200mg, Q3W plus LP002 of 5mg/kg, Q3W for up to 1 year. |
| Ib: Expansion | Experimental | Drug: HX008, Drug: LP002Approximately 30 participants will receive HX008 of 200mg, Q3W plus LP002 of the recommended dose, Q3W for up to 1 year. |
| Ib: Control | Experimental | Drug: LP002Approximately 15 participants will receive LP002 of recommended dose, Q3W for up to 1 year. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Provide written informed consent voluntarily. Understand this protocol and be willing and able to adhere to the study visit schedule.
- Male and Female aged 18 to 75 are eligible.
- Histologic diagnosis of locally advanced or metastatic melanoma, who are unable to undergo complete resection, while ocular melanoma is excluded, and the overall rate of mucosal melanoma is no more than 22%.
- Has experienced progressed disease in previous anti-PD-1 or PD-L1 therapy for the locally advanced or metastatic melanoma (anti-PD-1 or PD-L1 therapy as neo-adjuvant or adjuvant therapy could be accepted if progressed disease occured with 6 months after the last dose of treatment).
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
Key exclusion criteria (20 listed)
- Prior malignancy active within the previous 5 years except for locally curable cancers that have been apparently cured, such as carcinoma in situ of the cervix or basal cell skin cancer.
- Has experienced severe immunotherapy related toxicity in the previous anti-PD-1 / PD-L1 monoclonal antibody treatment, including but not limited to: Grade 3 / 4 pneumonia, proteinuria, uveitis or upper scleritis, myasthenia gravis, pancreatitis, hepatitis, bullous skin diseases (including SJS, TEN); grade 2-4 encephalitis, myocarditis; any grade of Guillain Barre syndrome, transverse myelitis; severe inflammatory arthritis that significantly impact the quality of patient's life;
- Known to has BRAF V600 mutation before signing informed consent form, and has not received any corresponding targeted therapy.
- With adverse reactions of previous treatment that have not recovered to CTCAE V5.0 grade ≤ 1, except for the residual hair loss effect.
- With active or history of autoimmune diseases that may recur (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, glomerulitis, etc.), or patients with high risk (e.g., organ transplantation requiring immunosuppressive therapy). While those with the following diseases were allowed to be enrolled: a) Stable patients with type I diabetes after a fixed dose of insulin; b) Autoimmune hypothyroidism requiring hormone replacement therapy only; c) Skin diseases requiring no systemic treatment (e.g. eczema, skin rash covering less than 10% of the body surface, psoriasis without ophthalmic symptoms, etc.).
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 |
|---|---|---|
| HX008HX008: 200mg, Q3W | Drug | Ia: LP002 dose escalation-1mg/kg, Ia: LP002 dose escalation-3mg/kg, Ia: LP002 dose escalation-5mg/kg, Ib: Expansion |
| LP002LP002: 1mg/kg, or 3mg/kg, or 5mg/kg, Q3W | Drug | Ia: LP002 dose escalation-1mg/kg, Ia: LP002 dose escalation-3mg/kg, Ia: LP002 dose escalation-5mg/kg, Ib: Control, Ib: Expansion |
Primary outcome
DLT (dose limited toxicity) rate
Time frame: 6 months
To observe how many participants experience DLT in each LP002 dose group in phase Ia.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: 2 years
Objective Response Rate (ORR)
Time frame: 1 year
Percentage of subjects achieving complete response (CR) and partial response (PR).
Terminal half-life (T1 / 2) of HX008 and LP002
Time frame: 1 year
Area under curve (AUC) of HX008 and LP002
Time frame: 1 year
Apparent volume of distribution of HX008 and LP002
Time frame: 1 year
Systemic clearance of HX008 and LP002
Time frame: 1 year
Cmax of HX008 and LP002
Time frame: 1 year
Cmin of HX008 and LP002
Time frame: 1 year
Tmax of HX008 and LP002
Time frame: 1 year
4 secondary outcomes
Disease Control Rate (DCR)
Time frame: 1 year
Duration of Response (DOR)
Time frame: 2 years
Progression-Free Survival (PFS)
Time frame: 2 years
Overall survival (OS)
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 16 Feb 2021.
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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.
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 HX008 and LP002 in people with Melanoma, run by Taizhou HoudeAoke Biomedical Co., Ltd. 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 11 inclusion and 20 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 16 Feb 2021. 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 Jun Guo, MD (010-88140650, guoj307@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DLT (dose limited toxicity) rate (time frame: 6 months). The study lists 10 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 16 Feb 2021.