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Advanced Solid TumorsPhase 2NCT04169672

Study of Surufatinib Single Agent or Surufatinib Combined With Toripalimab in Patients With Advanced Solid Tumors

A Phase 2 study testing Surufatinib and Toripalimab in people with Advanced Solid Tumors, run by Hutchison Medipharma Limited at 2 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a phase II, single arm, open-label, multicenter study to evaluate the efficacy and safety of Surufatinib single agent or Surufatinib combined with Toripalimab in patients with advanced solid tumors. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Advanced Solid Tumors
What is being tested?
Surufatinib and Toripalimab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
248 participants
Where
2 sitesChina
Study dates
26 Dec 2019to 28 Feb 2023
Phase
Phase 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

  • Adequately understand the study and voluntarily sign the Informed Consent Form;
  • 18-75 years old;
  • Histologically or cytologically confirmed advanced solid tumors (focusing on neuroendocrine neoplasmas (NENs), biliary tract cancer, gastric cancer, thyroid cancer, small cell lung cancer, non-small cell lung cancer, soft tissue sarcoma, endometrial cancer and esophageal squamous cell carcinoma, etc);
  • Fail or cannot tolerate the standard therapies, or for whom no effective standard therapy is available, or refuse standard therapy;
  • NSCLC cohort: no prior chemotherapy or any other systemic therapy for stage IV NSCLC with positove PD-L1 expression;
  • Have a performance status (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale;
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  • Have measurable lesions (according to RECIST 1.1);
  • Agree to provide histology samples;
  • Lab tests within 7 days before first dose:
  • Absolute neutrophil count (ANC) ≥1.5×10^9/L, platelet count ≥100×10^9/L, and hemoglobin ≥9 g/dL;
  • Serum total bilirubin <1.5 times the upper limit of normal (ULN);
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤ 1.5 times the ULN without liver metastases; and ALT and AST ≤ 3 times ULN with liver metastases;
  • Serum creatinine <1.5 times ULN and creatinine clearance ≥50 mL/min;
  • Urine protein < 2+; if ≥2+, 24-hour urine protein <1 g;
  • International Normalized Ratio (INR) ≤1.5 ULN and activated partial thromboplastin time (APTT) ≤1.5 ULN;
  • Have expected survival of more than 12 weeks;
  • Male or females patients with reproductive potential must agree to use an effective contraceptive method, for example, double-barrier device, condom, oral or injected birth control medication or intrauterine device, during the study and within 90 days after study treatment discontinuation. All female patients are considered to be fertile, unless the patient had natural menopause or artificial menopause or sterilization (such as hysterectomy, bilateral oophorectomy or ovarian irradiation).

Who cannot join

  • Toxicity from a previous anti-tumor treatment that does not return to Grade 0 or 1 (except for hair loss or Grade ≤ 2 peripheral neurotoxicity caused by oxaliplatin);
  • Other malignancies diagnosed within the previous 5 years, except skin basal cell carcinoma or skin squamous cell carcinoma or cervical carcinoma in situ;
  • Symptomatic central nervous system (CNS) metastasis or cancerous meningitis (meningeal metastasis) during the screening period;
  • Systematic anti-tumor therapy received within 4 weeks prior to first dose, including chemotherapy, biotherapy, targeted therapy, hormonotherapy, and anti-tumor Chinese medicine treatment;
  • Radical radiotherapy within 4 weeks prior to first dose, radioactive seed implantation within 60 days prior to first dose, or Palliative radiotherapy for a bone metastasis lesion within 1 week prior to first dose;
  • Functional NENs which need to be treated with long acting Somatostatin analogues (SSAs) to control disease related syndromes, such as insulinoma, gastrinoma, glucagonoma, somatostatinoma, ACTHoma, VIPoma, accompanied by carcinoid syndrome, Zollinger-Ellison syndrome or other active symptoms;
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  • Previously treated with anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody, anti-CTLA-4 antibody, any other antibody acting on the T cell stimulation or checkpoint pathway or Surufatinib;
  • Previously received anti-VEGF/VEGFR targeted drugs and progressed during the treatment or within 4 months after these drugs;
  • Thyroid dysfunction with symptoms or require treatment when screening except hypothyroidism controlled only by thyroid hormone replacement therapy, the level of TSH in patients with iodine refractory differentiated thyroid cancer is more than 0.1 mU/L (or other corresponding unit level) before the beginning of the study treatment;
  • Previously received immunosuppressive drugs except locally or temporarily used glucocorticoids;
  • Autoimmune disease with systematic treatment or autoimmune disease history within 2 years;
  • Previously received systematic immunologic stimulants within 4 weeks prior to the first dose;
  • Inoculated with any live vaccine or attenuated live vaccine within 4 weeks or planed to inoculate during the study;
  • Major surgery within 4 weeks or unhealed wound/fracture;
  • Uncontrolled malignant hydrothorax, ascites, or pericardial effusion;
  • Under anti-hypertension treatment, still uncontrolled hypertension, defined as: systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg;
  • Disease or situation that affects drug absorption, or unable to take drugs orally;
  • Previously received CYP3A4 strong inducers or strong inhibitors within 1 week or 5 half-life periods;
  • Active gastric and duodenal ulcers, ulcerative colitis and other digestive disease, gastrointestinal tumor with active bleeding, or other gastrointestinal conditions that may cause bleeding or perforation by investigator's discretion;
  • History or presence of a serious hemorrhage (>30 ml within 2 months), hemoptysis (>5 ml blood within 4 weeks) within 2 months;
  • History or presence of an artery thrombosis or deep venous thrombosis within 6 months, or a thromboembolic event (including transient ischemic attack) within 12 months;
  • Clinically significant cardiovascular disease, including but not limited to, acute myocardial infarction within 6 months prior to first dose, severe/unstable angina pectoris or coronary artery bypass grafting, congestive heart failure according to the New York Heart Association (NYHA) classification ≥ 2; ventricular arrhythmias which needs drug treatment; left ventricular ejection fraction (LVEF) <50%;
  • Severe electrolyte abnormalities with clinical significance by investigator's discretion;
  • Any clinically significant active infection, or unknown reason fever prior to first dose (temperature > 38.5℃);
  • Active tuberculosis, on treatment or previously received antituberculosis therapy within 1 year;
  • History or presence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia or severely injured lung function except radiation pneumonia in the radiotherapy area;
  • A positive immunodeficiency virus (HIV) test;
  • History of clinically significant hepatic disease, including, but not limited to, known hepatitis B virus (HBV) infection with HBV DNA positive (copies ≥1×10^3/ml or > 200 IU/ml); known Hepatitis C virus (HCV) infection with HCV RNA positive (copies ≥1×10^3/ml); or liver cirrhosis, etc.;
  • Previously received investigational treatments unlisted in China within 4 weeks prior to first dose;
  • Women who are pregnant or lactating;
  • Previously allergic to any of the JS001 or Surufatinib ingredients, or monoclonal antibody;
  • Any other conditions are inappropriate for the use of the investigational products by investigator's discretion.

Trial locations and contacts

2 sites in 1 country.

China2 sites

  • Beijing Cancer Hospital

    Beijing, Beijing Municipality, 100142

  • Fudan University Shanghai Cancer Center

    Shanghai, Shanghai Municipality, 200032

Other trials in China

About this study

Official title: A Phase II, Open-label, Single-arm, Multi-center Study of the Efficacy and Safety of Surufatinib Single Agent or Surufatinib Combined With Toripalimab in Patients With Advanced Solid Tumors

This is a phase II, single arm, open-label, multicenter study to evaluate the efficacy and safety of Surufatinib single agent or Surufatinib combined with Toripalimab in patients with advanced solid tumors.

Read the detailed description

The study population is about 260 patients with advanced solid tumors, who fails or can not tolerate standard therapies, or for whom no effective standard therapy is available, or who refuses standard therapies. This study includes two arms. One is that Surufatinib single agent 300mg once a day (QD) will be orally administrated in patients with advanced neuroendocrine carcinoma (NEC). In another arm Surufatinib 250 mg QD will be orally administrated and Toripalimab 240mg will be intravenously administered every 3 weeks up to documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent. For Toripalimab, the upper time limit for treatment is 2 years. The primary objective is safety of safety run-in (about 6 patients) and objective response rate (ORR) of Surufatinib single agent in patients with advanced NEC or Surufatinib combined with Toripalimab in patients with advanced solid tumors.

Being tested
Surufatinib, Toripalimab

What participants receive

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

  • SurufatinibDrug

    Also called HMPL-012

    Surufatinib is a tablet in the form of 50mg, oral, once a day.

  • ToripalimabDrug

    Also called JS001

    Toripalimab is an injection in the form of 240mg, intravenous, once three weeks.

Study groups in NCT04169672
Study groupRoleWhat they receive
Surufatinib & ToripalimabExperimentalSurufatinib 250mg will be taken orally once daily continuously through a 21-day cycle of study treatment. Toripalimab 240mg will be intravenously administered on Day 1 of each cycle.
Receives: Drug: Surufatinib; Drug: Toripalimab
SurufatinibExperimentalSurufatinib 300mg will be taken orally once daily continuously through a 21-day cycle of study treatment.
Receives: Drug: Surufatinib

What is being measured

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

  1. Adverse events (AEs) of safety run-in part

    The AEs of the first 6 patients were evaluated by the possibly occurs Dose Limited Toxicity (DLT).

    Measured: From Cycle 1 Day 1 to the end of Cycle 2 Day 7 (each cycle is 21 days)

  2. Objective response rate (ORR)

    The incidence of confirmed complete response or partial response (RECIST1.1).

    Measured: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy(up to approximately 2 years)

Secondary outcomes (9)

  1. Objective Response Rate (ORR)

    The incidence of confirmed complete response or partial response (irRECIST).

    Measured: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy(up to approximately 2 years)

  2. Duration of Response (DoR) (RECIST1.1 and irRECIST)

    Duration from the first time reported partial response or complete response to the first time of disease progression or death.

    Measured: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years)

  3. Progression-free Survival (PFS) (RECIST1.1 and irRECIST)

    A duration from the date of initial treatment with Surufatinib combined with Toripalimab to disease progression or death of any cause.

    Measured: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years)

  4. Disease Control Rate (DCR) (RECIST1.1 and irRECIST)

    Proportion of patients whose tumor volume control (reduced or enlarged) reaches a predetermined value and can maintain a minimum time limit.

    Measured: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years)

  5. Overall Survival (OS)

    Duration from the date of initial treatment with Surufatinib plus toripalimab to the date of death due to any cause.

    Measured: From date of first dose of study drug until withdrawal of consent or death (up to approximately 2 years)

  6. The AEs of all population

    An AE is any untoward medical occurrence in a patient or clinical investigation participant administered an investigational product.Safety and tolerance evaluated by incidence, severity and outcomes of AEs

    Measured: For each participant, from the first participant first dose until 30 days after the last dose (up to approximately 2 years)

  7. Anti-drug Antibody (ADA) of Toripalimab

    Blood samples will be collected and analyzed. Serum ADA will be detected by using validated methods.

    Measured: half of hour predose of Toripalimab for Cycle 1, 2, 3, 4, 5 (each cycle is 21 days) and 30 days after the last dose

  8. Plasma maximum Concentration (Cmax)

    Blood samples will be collected at the designated time points.Cmax is the highest concentration of drug in the blood that is measured after a dose.

    Measured: Surufatinib (Cycle 1 and 3): Day 1: predose;1, 2, 4, 8,12 and 24 hours postdose. Toripalimab (Cycle 1 and 3): predose; 0.5, 2, 6, 12,24,48,96,168,336 and 504 hours postdose

  9. The drug concentration-time curve (AUC)

    Plasma samples will be collected at the designated time points. AUC represents the overall amount of drug in the bloodstream after dosing.

    Measured: Surufatinib (Cycle 1 and 3): Day 1: predose;1, 2, 4, 8,12 and 24 hours postdose. Toripalimab (Cycle 1 and 3): predose; 0.5, 2, 6, 12,24,48,96,168,336 and 504 hours postdose

Timeline

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

  1. First posted20 Nov 2019
  2. Study start26 Dec 2019
  3. Primary completion28 Feb 2023
  4. Study completion28 Feb 2023

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
248 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04169672
Sponsor's protocol ID
2019-012-00CH1
Status last verified
Mar 2023
First submitted
18 Nov 2019
Last updated
2 Mar 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Zhang P, Chen Z, Shi S, Li Z, Ye F, Song L, Zhang Y, Yin F, Zhang X, Xu J, Cheng Y, Su W, Shi M, Fan S, Tan P, Zhong C, Lu M, Shen L. Efficacy and safety of surufatinib plus toripalimab, a chemotherapy-free regimen, in patients with advanced gastric/gastroesophageal junction adenocarcinoma, esophageal squamous cell carcinoma, or biliary tract cancer. Cancer Immunol Immunother. 2024 May 7;73(7):119. doi: 10.1007/s00262-024-03677-7.

    PubMed 38713205

  • Zhang P, Shi S, Xu J, Chen Z, Song L, Zhang X, Cheng Y, Zhang Y, Ye F, Li Z, Yin F, Ji D, Gao H, Li Y, Chen W, Yang M, Weng D, Wu C, Ma Y, Sheng W, Zhao Y, Yin X, Shen W, Su W, Shi M, Fan S, Tan P, Xu Q, Lu M, Shen L. Surufatinib plus toripalimab in patients with advanced neuroendocrine tumours and neuroendocrine carcinomas: An open-label, single-arm, multi-cohort phase II trial. Eur J Cancer. 2024 Mar;199:113539. doi: 10.1016/j.ejca.2024.113539. Epub 2024 Jan 15.

    PubMed 38237373

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Surufatinib and Toripalimab in people with Advanced Solid Tumors, run by Hutchison Medipharma Limited at 2 sites 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 17 inclusion and 32 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: finished, as of the sponsor's last update on 2 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Adverse events (AEs) of safety run-in part (time frame: From Cycle 1 Day 1 to the end of Cycle 2 Day 7 (each cycle is 21 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?

On the ClinicalTrials.gov record for NCT04169672, 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 2 Mar 2023.

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