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
Overview
- Phase
- Phase 2
- Intervention
- Surufatinib
- Conditions
- Advanced Solid Tumors
- Sponsor
- Hutchison Medipharma Limited
- Enrollment
- 248
- Locations
- 2
- Primary Endpoint
- Adverse events (AEs) of safety run-in part
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief 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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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;
- •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;
Exclusion Criteria
- •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;
- •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;
Arms & Interventions
Surufatinib & Toripalimab
Surufatinib 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.
Intervention: Surufatinib
Surufatinib & Toripalimab
Surufatinib 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.
Intervention: Toripalimab
Surufatinib
Surufatinib 300mg will be taken orally once daily continuously through a 21-day cycle of study treatment.
Intervention: Surufatinib
Outcomes
Primary Outcomes
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 AEs of the first 6 patients were evaluated by the possibly occurs Dose Limited Toxicity (DLT).
Objective response rate (ORR)
Time Frame: From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy(up to approximately 2 years)
The incidence of confirmed complete response or partial response (RECIST1.1).
Secondary Outcomes
- Duration of Response (DoR) (RECIST1.1 and irRECIST)(From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years))
- Objective Response Rate (ORR)(From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy(up to approximately 2 years))
- The AEs of all population(For each participant, from the first participant first dose until 30 days after the last dose (up to approximately 2 years))
- Progression-free Survival (PFS) (RECIST1.1 and irRECIST)(From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years))
- Overall Survival (OS)(From date of first dose of study drug until withdrawal of consent or death (up to approximately 2 years))
- Disease Control Rate (DCR) (RECIST1.1 and irRECIST)(From date of first dose of study drug until disease progression, withdrawal of consent, death, new anti-cancer therapy (up to approximately 2 years))
- Anti-drug Antibody (ADA) of Toripalimab(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)
- Plasma maximum Concentration (Cmax)(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)
- The drug concentration-time curve (AUC)(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)