Tumor, SolidPhase 1NCT03491631
Phase I Study of SHR9146 + SHR-1210 +/- Apatinib in Patients With Advanced Solid Tumors
A Phase 1 study testing SHR9146+SHR-1210 and SHR9146+SHR-1210+Apatinib in people with Tumor, Solid and Cancer, Metastatic, run by Jiangsu HengRui Medicine Co., Ltd. at 1 site in China.
Trial summary
This phase I trial is designed to efficiently identify the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) for the combination therapy regimen of the IDO1 inhibitor SHR9146 when administered in combination with immune checkpoint PD-1 inhibitor SHR-1210 plus VEGFR inhibitor Apatinib or not in subjects… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Tumor, Solid, Cancer, Metastatic, Neoplasm Malignant
- What is being tested?
- SHR9146+SHR-1210 and SHR9146+SHR-1210+Apatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteChina
- Study dates
- 20 Nov 2018to Sep 2023
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (including subject refusal or intolerance).
- At least one measurable parameter according to RECIST 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Life expectancy of at least 12 weeks.
- Subjects must have normal organ and marrow function as defined below:
- Absolute neutrophil count > 1,500/mcL
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- Platelets > 100,000/mcL
- Total bilirubin ≤ 1.5 times the upper limit of normal (ULN); for subjects with liver metastases, Total bilirubin≤ 2 x ULN,
- AST/ALT (SGOT/SGPT) ≤ 2.5 times institutional normal limits; for subjects with liver metastases, ALT and AST ≤ 5 × ULN
- Creatinine ≤ 1.5 times the ULN
- Subjects with known brain metastases will only be eligible after their tumors have been treated with definitive resection and/or radiotherapy and they are neurologically stable for at least two months apart and at least 1 month off steroids.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Known history of hypersensitivity to any components of SHR9146 and SHR-1210 formulation, or other antibody formulation.
- Prior exposure to any T cell co-stimulatory therapy or immune checkpoint inhibitors, including but not limited to other anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-PD-L2 antibodies.
- Prior systemic chemotherapy, radiotherapy, immunotherapy, hormone therapy, surgery or target therapy within 4 weeks (Or 5 half-life of the drug, calculate the longer ) before the study drug administration, or any unresolved AEs > Common Terminology Criteria for Adverse Events (CTCAE) Grade 1.
- Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded.
- Active brain metastasis or meningeal metastasis.
- Clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, or coronary artery bypass surgery, Congestive heart failure (New York heart association (NYHA) class > 2), ventricular arrhythmia which need medical intervention.
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- Any other medical, psychiatric, or social condition deemed by the investigator to be likely to interfere with a subject's rights, safety, welfare, or ability to sign informed consent, cooperate, and participate in the study or would interfere with the interpretation of the results.
- Severe or uncontrolled systemic disease such as clinically significant hypertension(systolic pressure >/= 140 mm Hg and/or diastolic pressure >/= 90 mm Hg). (group 2)
- Previous digestive tract bleeding history within 3 months or evident gastrointestinal bleeding tendency, such as: esophageal varices, local active ulcerative lesions, gastric ulcer and duodenal ulcer, the ulcerous colitis, gastrointestinal diseases such as portal hypertension or resection of tumor with bleeding risk, etc. (group 2)
- Previous Arterial/venous thrombosis events within 3 months. (group 2)
- Proteinuria ≥ (++) or 24 hours total urine protein > 1.0 g. (group 2)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Study to Characterize the Tolerance, Safety, Pharmacokinetics/Pharmacodynamics and Effect of PD-1 Inhibitor SHR-1210 in Combination With IDO Inhibitor SHR9146 and With/Without Apatinib in Patients With Advanced Solid Tumors (PIANO)
This phase I trial is designed to efficiently identify the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) for the combination therapy regimen of the IDO1 inhibitor SHR9146 when administered in combination with immune checkpoint PD-1 inhibitor SHR-1210 plus VEGFR inhibitor Apatinib or not in subjects with advanced/metastatic solid tumors. All subjects will receive the same standard SHR-1210 plus Apatinib (only three drugs group)regimen, while SHR9146 in doses increasing from 100 mg twice daily to, potentially, 600 mg twice daily. Once the recommended regimen has been identified, subjects with the selected tumor type will be enrolled into expansion cohorts based upon prior safety and tolerability data.
- Conditions
- Tumor, Solid, Cancer, Metastatic, Neoplasm Malignant
- Being tested
- SHR9146+SHR-1210, SHR9146+SHR-1210+Apatinib
- Medical subject headings
- Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SHR9146+SHR-1210Drug
SHR9146: Initial dose of 100mg BID with escalation planned to 600mg BID; SHR-1210: 200mg Q2W
SHR9146+SHR-1210+ApatinibDrug
SHR9146: Initial dose of 100mg BID with escalation planned to 600mg BID; SHR-1210: 200mg Q2W Apatinib:250mg QD
| Study group | Role | What they receive |
|---|---|---|
| 2 drugs combination group | Experimental | Not described Receives: Drug: SHR9146+SHR-1210 |
| 3 drugs combination group | Experimental | Not described Receives: Drug: SHR9146+SHR-1210+Apatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT
Measured: Baseline through 27/28 days
MTD
Measured: Baseline through 27/28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2018
- Study start20 Nov 2018
- Primary completionJun 2023 (estimated)
- Study completionSep 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tumor, SolidStudies of the same condition, open and under way.
- More trials run by Jiangsu HengRui Medicine Co., Ltd.The 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
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ying Cheng, Prof., Principal investigator, Jilin Provincial Tumor Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03491631
- Sponsor's protocol ID
- SHR9146-I-101
- Status last verified
- Nov 2022
- First submitted
- 1 Apr 2018
- Last updated
- 4 Nov 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study to Characterize the Tolerance, Safety, Pharmacokinetics/Pharmacodynamics and Effect of PD-1 Inhibitor SHR-1210 in Combination With IDO Inhibitor SHR9146 and With/Without Apatinib in Patients With Advanced Solid Tumors (PIANO)
- ClinicalTrials.gov ID
- NCT03491631
- Acronym / sponsor ID
- SHR9146-I-101
- Conditions
- Tumor, Solid, Cancer, Metastatic, Neoplasm Malignant
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Jiangsu HengRui Medicine Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 20 Nov 2018 (actual)
- Primary completion
- Jun 2023 (estimated)
- Study completion
- Sep 2023 (estimated)
- First posted
- 9 Apr 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 phase I trial is designed to efficiently identify the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) for the combination therapy regimen of the IDO1 inhibitor SHR9146 when administered in combination with immune checkpoint PD-1 inhibitor SHR-1210 plus VEGFR inhibitor Apatinib or not in subjects with advanced/metastatic solid tumors. All subjects will receive the same standard SHR-1210 plus Apatinib (only three drugs group)regimen, while SHR9146 in doses increasing from 100 mg twice daily to, potentially, 600 mg twice daily. Once the recommended regimen has been identified, subjects with the selected tumor type will be enrolled into expansion cohorts based upon prior safety and tolerability data.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 2 drugs combination group | Experimental | Drug: SHR9146+SHR-1210 |
| 3 drugs combination group | Experimental | Drug: SHR9146+SHR-1210+Apatinib |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (including subject refusal or intolerance).
- At least one measurable parameter according to RECIST 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Life expectancy of at least 12 weeks.
- Subjects must have normal organ and marrow function as defined below:
Key exclusion criteria (11 listed)
- Known history of hypersensitivity to any components of SHR9146 and SHR-1210 formulation, or other antibody formulation.
- Prior exposure to any T cell co-stimulatory therapy or immune checkpoint inhibitors, including but not limited to other anti-CTLA-4, anti-PD-1, anti-PD-L1 and anti-PD-L2 antibodies.
- Prior systemic chemotherapy, radiotherapy, immunotherapy, hormone therapy, surgery or target therapy within 4 weeks (Or 5 half-life of the drug, calculate the longer ) before the study drug administration, or any unresolved AEs > Common Terminology Criteria for Adverse Events (CTCAE) Grade 1.
- Patients with any active autoimmune disease or history of autoimmune disease, including but not limited to the following: hepatitis, pneumonitis, uveitis, colitis (inflammatory bowel disease), hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism, except for subjects with vitiligo or resolved childhood asthma/atopy. Asthma that requires intermittent use of bronchodilators or other medical intervention should also be excluded.
- Active brain metastasis or meningeal metastasis.
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 |
|---|---|---|
| SHR9146+SHR-1210SHR9146: Initial dose of 100mg BID with escalation planned to 600mg BID; SHR-1210: 200mg Q2W | Drug | 2 drugs combination group |
| SHR9146+SHR-1210+ApatinibSHR9146: Initial dose of 100mg BID with escalation planned to 600mg BID; SHR-1210: 200mg Q2W Apatinib:250mg QD | Drug | 3 drugs combination group |
Primary outcome
DLT
Time frame: Baseline through 27/28 days
MTD
Time frame: Baseline through 27/28 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2022.
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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.
Ying Cheng, Prof. principal investigator
Jilin Provincial Tumor Hospital
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 SHR9146+SHR-1210 and SHR9146+SHR-1210+Apatinib in people with Tumor, Solid and Cancer, Metastatic, run by Jiangsu HengRui Medicine 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 12 inclusion and 11 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 4 Nov 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 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?
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?
DLT (time frame: Baseline through 27/28 days). 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 4 Nov 2022.