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Solid TumorPhase 1NCT03182673

The Study of SHR7390 in Combination With SHR-1210 and SHR3162 in Patients With Advanced Solid Tumors

A Phase 1 study testing SHR7390, SHR-1210 and SHR3162 in people with Solid Tumor, run by Jiangsu HengRui Medicine Co., Ltd. at 1 site in China.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The study consists of the two parts, the first one is SHR7390 combined with SHR-1210, the second one is SHR7390 combined with SHR-1210 and SHR3162. Two parts of the study are separately to assess the safety and tolerability, to define dose limiting toxicity（DLT) and maximum tolerated dose (MTD),to evaluate the… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Solid Tumor
What is being tested?
SHR7390, SHR-1210 and SHR3162
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
1 siteChina
Study dates
24 Jul 2017to 12 Jun 2019
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

  • The study is open to all males and females who meet the following inclusion criteria at screening and baseline to participate in the study.
  • To be included to participate in this study each patient must:
  • 18-70 years of age, both male and female;
  • The invalid standard treatment or non standard and effective treatment in patients with advanced solid tumors diagnosed by pathology;
  • （1) in the phase of dose escalation , the subjects with RAS or BRAF mutation status and microsatellite stability （MSS）are not restricted.
  • （2）in the phase of dose expansion，the subjects with RAS or BRAF mutations and microsatellite stability (MSS) are included necessarily.
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  • （3) the subjects included in the phase of dose expansion must have at least one measurable target lesion with RECIST V 1.1.
  • If they in the phase of dose expansion are unable to provide the results of previous RAS/BRAF mutation and microsatellite stability,subjects must provide previous cancer tissues（paraffin blocks or pathological 8-10 white sections）, or fresh biopsy specimens.
  • 3. The Eastern Cooperative Oncology Group （ECOG） General status (performance status, PS) of 0-1;
  • 4. The expected lifetime ≥ 3 months;
  • 5. The organ function must meet the following requirements:
  • Adequate bone marrow reserve: including neutrophil absolute count,platelets and hemoglobin;
  • Liver: serum albumin ≥ 2.8 g/dl; bilirubin≤1.5 upper limit of normal value (ULN), Alanine aminotransferase（ALT）and aspartate aminotransferase（AST）≤ 2.5 upper limit of normal value (ULN),if there is liver metastasis, the ALT or AST≤5xULN;
  • Kidneys: creatinine clearance ≥ 50 mL/min (Cockcroft-Gault of the standard formula）；
  • Heart: left ventricular ejection fraction ≥ 50%; normal Electrocardiograph (ECG) and corrected QT interval（QTc）;male QTc<450ms，female QTc<470ms
  • 6. The lesion of the patients caused by other treatments has been restored(≤1 grade，except alopecia and other adverse events that the investigators judged to be tolerable）。The time interval between previous treatment and the first use of study drugs：nitrosourea or mitomycin> 6 weeks; cytotoxic drugs, monoclonal antibodies, radiotherapy or surgery> 4 weeks; TKI targeted drugs> 2 weeks;endocrine therapy> 1 week；
  • 7. A agreement to use a highly effective, non-hormonal form of contraception is required for women of childbearing potential and men with partners of childbearing potential, who were not sterilized surgically, for duration of the study treatment and after the last dose of study treatment; For female patients of child bearing potential,who was not sterilized surgically,the serum human chorionic gonadotropin （HCG） pregnancy test must be the negative
  • 8. Voluntary ability to follow the procedures of clinical study. Written informed consent is provided by signing the informed consent form.

Who cannot join

  • Previous treatment with any other tumor immune checkpoint inhibitors within 2 months before the first use of study drugs；previous treatment with other MEK inhibitors or PARP inhibitors (the previous treatment of PARP inhibitors is only excluded in the second part of the study).
  • Use of other investigational anti-cancer drugs or the termination of the investigational drugs within the last four weeks.
  • The subjects had active autoimmune diseases, a history of immunodeficiency disease and autoimmune diseases, or a history of disease or syndrome with systemic steroid hormones or immunosuppressive drugs(such as asthma, idiopathic pulmonary fibrosis, institutional pneumonia, bronchiolitis obliterans, and drug pneumonia,idiopathic pneumonia or interstitial pneumonia, colitis, hepatitis, pituitary inflammation, vasculitis, nephritis,hyperthyroidism, hypothyroidism, but not limited to these diseases or syndromes），or other acquired (HIV) and congenital immunodeficiency diseases, or a history of organ transplantation (including allogeneic bone marrow transplantation).
  • Known severe hypersensitivity or other hypersensitivity to chimeric or humanized antibodies or fusion proteins; known to be allergic or hypersensitive to components of SHR-1210，SHR7390 or SHR3162.
  • The subjects were known to have tumor metastases of central nervous system or meningeal metastases, or a history of primary tumors of CNS.
  • Presence of a factor that influences the oral drug (such as inability to swallow) or presence of active gastrointestinal disease or other diseases that will interfere significantly with the absorption, distribution, metabolism, or excretion of drug.
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  • History of the retinopathy or the sensory retinal detachment. As assessed by ophthalmologist, presence of the risk factors of study treatment that may cause retinal vein thrombosis/occlusion (RVO), central serous chorioretinopathy (CSCR),or neovascular and macular degeneration.
  • The intraocular pressure > 21mmHg or glaucoma was diagnosed within 4 weeks
  • The evidence of severe or uncontrollable pleural effusion, peritoneal effusion or pericardial effusion. The clinical treatment is required, such as periodic drainage.
  • The evidence of severe or uncontrolled systemic diseases (e.g. chronic lung, liver, kidney, or heart diseases).
  • Unstable angina pectoris or new angina pectoris within recent three months.Presence of arrhythmia, myocardial ischemia with long-term drug treatment.III-IV stage heart failure as defined by the New York Heart Association (NYHA). Presence of acute myocardial infarction events and congestive heart failure within the first six months before screening.
  • Medical treatment for an acute stage of infection or active TB.
  • Hepatitis B virus（HBV) or hepatitis C virus (HCV) infection stage with abnormal liver function.
  • Pregnant or lactating women or intending to become pregnant during the study period.
  • Living attenuated vaccines within one months of the initial use of the drug, or a living attenuated vaccine is expected during the study period.
  • A history of neurological or psychiatric disorders, and a history of psychotropic substance or drug abuse.
  • According to the judgement of the investigators, presence of serious hazards to the safety of the subjects, the concomitant diseases confusing to analyze the study data or influencing to complete this study (such as severe hypertension, diabetes, thyroid disease, etc.),or any other situation.

Trial locations and contacts

1 site in 1 country.

China1 site

  • The Cancer Center,Sun Yat-sen University

    Guangzhou, Guangdong, 510060

Other trials in China

About this study

Official title: A Phase I, Open Label, Dose Escalation/Expansion Study to Evaluate the Safety, Tolerability and Pharmacokinetics of SHR7390 Combined With SHR-1210 and SHR3162 in Patients With Advanced Solid Tumors

The study consists of the two parts, the first one is SHR7390 combined with SHR-1210, the second one is SHR7390 combined with SHR-1210 and SHR3162. Two parts of the study are separately to assess the safety and tolerability, to define dose limiting toxicity（DLT) and maximum tolerated dose (MTD),to evaluate the pharmacokinetics ,to assess the antitumor activity in patients with advanced solid tumors preliminarily and to recommend reasonable dosage regimen of SHR7390 for the follow-up clinical trial.

Read the detailed description

This is a phase I, open-label,two parts,dose escalation/expansion clinical study.The safety,tolerance,PK and preliminary efficacy of two-drug combination and three-drug combination were evaluated respectively in the patients with advanced solid tumors that have no any targeted agents as the standard therapies.

In the first study part, subjects receiving a single dose of SHR7390 (Run-in) are observed in 7-10 days, then accepted two drug combination therapy, SHR7390 is administered once daily orally for 28 days for a treatment cycle. At the same time, SHR-1210 was given intravenously per 2 weeks at the fixed dose of 200mg.

In the second study part, subjects accepted three drug combination therapy, SHR7390 is administered orally for 21 days and discontinued for 7 days in a 28-day treatment cycle,SHR3162 was administered orally twice a day for 28 days at a fixed dose of 100 mg. At the same time, SHR-1210 was given intravenously per 2 weeks at the fixed dose of 200mg.

Dose limiting toxicities (DLT) in the first study part will be assessed during the Run-in and first cycle of treatment. the dose escalation is designed by Accelerated Titration Designs during initial accelerated phase. when the significant toxicity or DLT is observed in the Run-in and first cycle of treatment,the accelerated titration trial terminates and subsequent dose escalations are become a conventional design of 3+3 patients. If one adverse event （AE） meets dose limiting toxicity (DLT) criteria at a given dose, 3 additional patients will be enrolled in this dose cohort. If 2 DLTs are determined at a given dose level, the previous dose will be designated as the MTD.

Based on preliminary determination of RP2D and sufficient safety data in the first part of the study, the second part of three-drug combination will be carried out. the preset dose of SHR7390 includes RP2D initially determined in the first part of the study and its previous low dose level (for example, RP2D is 0.5 mg/d, while the former low dose is 0.25 mg/d). Dose escalation is a conventional design of 3+3 patients.

Additional patients will be enrolled for pharmacokinetic (PK) evaluations at different dose levels based on preliminary safety and tolerability.Each dose level can expand at least 12 subjects , of which 9-12 subjects are PK subjects. Multiple blood samples at designated time points will be collected for PK evaluations (more than 12 subjects are determined by SMC).

The safety, tolerability and AEs will be closely monitored throughout the study duration. The preliminary effectiveness and clinical benefits of two-drug combination and three-drug combination will be evaluated.

Conditions
Solid Tumor
Being tested
SHR7390, SHR-1210, SHR3162
Keywords
advanced solid tumor, Protein Kinase MEK inhibitor (MEKi), Programmed Death 1(PD-1), Safety, Pharmacokinetics, PARP inhibitor

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SHR7390Drug

    Also called MEKi

    SHR7390 is provided as white, film-coated,immediate release tablets containing SHR7390 at dosage strengths of 0.125 mg,0.5 mg and 2mg. Multiple tablets of SHR7390 will be administered orally to achieve targeted doses of SHR7390: 0.125 mg-4 mg. Tablets will be administered once daily or for 21 days and discontinued for 7 days with 240 ml water after 2 hours of the meal.

  • SHR-1210Biological

    Also called PD-1

    SHR-1210 is a humanized anti-PD1 immunoglobulin G4 (IgG4) monoclonal antibody. SHR-1210 is provided as the lyophilized powder,200 mg/vial.SHR-1210 was given with 200mg fixed dose intravenously per 2 weeks at the D1 and D15.Intravenous infusion over 30 min

  • SHR3162Drug

    Also called parp inhibitor

    SHR3162 is provided as capsules containing SHR3162 at dosage strengths of 10mg,40mg and 100mg. The capsule of SHR3162 will be orally administered with 240ml water twice a day to achieve targeted doses of SHR3162 and the interval of SHR3162 capsules taken twice a day is about 12 hours.

Study groups in NCT03182673
Study groupRoleWhat they receive
SHR7390, SHR-1210 and SHR3162ExperimentalTotal 60-100 subjects with advanced solid tumors In the two-drug combination therapy,subjects were received single oral doses of SHR7390，then accepted two drug combination therapy, SHR7390 is administered multiple daily oral doses of SHR7390 for 28 days for a treatment cycle. At the same time, SHR-1210 was given intravenously per 2 weeks at the 200mg fixed dose. In the second study part, subjects accepted three drug combination therapy, SHR7390 is administered orally for 21 days and discontinued for 7 days in a 28-day treatment cycle,SHR3162 was administered orally twice a day for 28 days at a fixed dose of 100 mg. At the same time, SHR-1210 was given intravenously per 2 weeks at the 200mg fixed dose
Receives: Drug: SHR7390; Biological: SHR-1210; Drug: SHR3162

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity(DLT)

    A DLT is considered at AE related to study drug unless there is a clear, well-documented, alternative explanation for the toxicity. Severity of AEs are graded according to the NCI CTCAE 4.03 for the study, the occurrence of the following drug related AEs during the single dose and the first cycle(35-38 days,two-drug combination) or the first cycle (28 days, three-drug combination) will be considered a DLT by the investigator and SMC.

    MTD is the highest dose of SHR7390 in subjects with DLT less than 33.3% during the DLT observation in the dose escalation of two-drug combination.

    Measured: up to 24 months

Secondary outcomes (14)

  1. The assessment of Treatment-related Adverse Events

    Assessment of the incidence and severity of treatment-related AEs in all subjects who received at least 1 dose of SHR7390,SHR-1210 and SHR3162.

    Measured: Up to 24 months

  2. Time to peak (Tmax) of plasma concentration

    Pharmacokinetics profile of SHR7390:Time to peak (Tmax) of plasma concentration

    Measured: up to 24 months

  3. Maximum plasma concentration (Cmax)

    Pharmacokinetics profile of SHR7390: Maximum plasma concentration (Cmax)

    Measured: up to 24 months

  4. Halflife (T1/2)

    Pharmacokinetics profile of SHR7390: Halflife (T1/2)

    Measured: up to 24 months

  5. Clearance/ bioavailability (CL/F)

    Pharmacokinetics profile of SHR7390: Clearance/ bioavailability (CL/F)

    Measured: up to 24 months

  6. apparent volume of distribution/bioavailability (Vd/F)

    Pharmacokinetics profile of SHR7390: apparent volume of distribution/bioavailability (Vd/F)

    Measured: up to 24 months

  7. Area under curve (AUC)

    Pharmacokinetics profile of SHR7390: Area under curve (AUC)

    Measured: up to 24 months

  8. Accumulation index (Rac)

    Pharmacokinetics profile of SHR7390: Accumulation index (Rac)

    Measured: up to 24 months

  9. blood concentration of SHR7390

    Pharmacokinetics profile of SHR7390:blood concentration

    Measured: up to 24 months

  10. plasma concentration of SHR7390

    Pharmacokinetics profile of SHR7390:plasma concentration

    Measured: up to 24 months

  11. plasma concentration of SHR3162

    Pharmacokinetics profile of SHR3162: plasma concentration

    Measured: up to 24 months

  12. serum concentration of SHR-1210

    Pharmacokinetics profile of SHR-1210: serum concentration

    Measured: up to 24 months

  13. Efficacy Assessments

    Subjects will be assessed using RECIST v1.1. The primary aim is to demonstrate clinically meaningful improvement in ORR.

    Measured: up to 24 months

  14. The identification of the recommended Phase 2 dose (RP2D) of SHR7390 in subjects with advanced solid tumors

    When the dose escalation is accomplished, RP2D will be identified by the characterization of safety.

    Measured: up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jun 2017
  2. Study start24 Jul 2017
  3. Primary completion12 Jun 2019
  4. Study completion12 Jun 2019

Why it stopped: Sponsor R \& D Strategy Adjustment

Resources

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
Model description
SHR7390,SHR-1210 and SHR3162
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03182673
Sponsor's protocol ID
SHR7390-I-102-AST
Status last verified
Feb 2018
First submitted
7 Jun 2017
Last updated
1 Sep 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing SHR7390, SHR-1210 and SHR3162 in people with Solid Tumor, 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 18 inclusion and 17 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: stopped early, as of the sponsor's last update on 1 Sep 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?

The study was stopped early (reason given: Sponsor R \& D Strategy Adjustment). 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?

Maximum Tolerated Dose (MTD) and Dose-Limiting Toxicity(DLT) (time frame: up to 24 months). 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 NCT03182673.

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 1 Sep 2022.

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