Advanced Solid Tumors MedDRA version: 21.0 Level: PT Classification code 10061451 Term: Colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10052399 Term: Neuroendocrine tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10059514 Term: Small cell lung cancer metastatic Syste
Conditions
Interventions
Product Name: Surufatinib
Product Code: HMPL-012
Pharmaceutical Form: Capsule
INN or Proposed INN: Surufatinib
CAS Number: 1308672-74-3
Current Sponsor code: HMPL-012
Other descriptive name: Sulfatini
Sponsors
Hutchison MediPharma Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing, able to provide informed consent signed by study patient or legally acceptable representative, as specified by health authorities and institutional guidelines 2.=18 years of age 3.Part 1:have evaluable lesions(according to Response Evaluation Criteria in Solid Tumors version 1.1[RECIST v1.1]) Part 2:have measurable lesions(according to RECISTv1.1) 4.Absolute neutrophil count (ANC) of =1.5×109/L, platelet count of =100×109/L, and hemoglobin =9 g/dL 5.Serum total bilirubin (TBIL) <1.5 times the upper limit of normal (ULN) 6.Proteinuria <2+ by urinalysis;if proteinuria =2+, proteinuria <1 g by 24-hour urinary protein test is required 7.Patients without liver metastases must have alanine aminotransferase (ALT) and/or AST levels=2.5 times the ULN.Patients with liver metastases must have ALT and AST levels =5 times the ULN 8.Creatinine clearance =45 mL/min as calculated by the Cockcroft-Gault formula 9.International normalized ratio (INR) =1.5×ULN and activated partial thromboplastin time (aPTT) =1.5×ULN,unless the patient is currently receiving anticoagulants for prophylactic purposes 10.Have a performance status of 0 or 1 on the ECOG scale 11.Female patients of childbearing potential and male patients with partners of childbearing potential agree to use a highly effective form(s) of contraception that results in a low failure rate when used consistently and correctly Dose Escalation 12.Histologically or cytologically documented,locally advanced or metastatic solid malignancy of any type that has progressed on or are intolerant of standard therapies and for which no curative therapy exists Dose Expansion 13.Histologically or cytologically documented, locally advanced or metastatic a.Cohort A:adenocarcinoma of the colon or rectum that is microsatellite stable.Patients must have progressed on, or had discontinued due to intolerable toxicity to the following agents: fluoropyrimidine, oxaliplatin, irinotecan,an anti-VEGF targeted therapy,and if RAS wild-type and anti epidermal growth factor receptor antibody therapy.Treatment progression is defined as disease progression during or within 3 months after the last dose of standard therapy.Prior therapy could have included adjuvant chemotherapy if a tumor had recurred within 6 months after the last administration of treatment.Patients must have been previously treated with fluoropyrimidine-,oxaliplatin-,and irinotecan-based chemotherapy;an anti-VEGF biological therapy;and,if RAS wild-type,an anti-epidermal growth factor receptor antibody therapy a.Cohort B:progressive, low, or intermediate grade(Grade 1 or Grade 2)NETs of thoracic(B1) or GEP(B2) origins.Patients must have radiological documentation of progression of disease in the last 6 months prior to the initiation of study treatment and must have progressed on at least 1 line of standard therapy for metastatic disease i.For NETs originating from the thorax A.Grade 1 is defined as<2 mitoses/10 high-power field(HPF) and no necrosis B.Grade 2 is defined as2-10/10HPF and/or foci of necrosis ii.For NETs originating from GEP A.Grade 1 is defined as <2 mitoses/10 HPF and/or<3% Ki-67 index B.Grade 2 is defined as 2-20/10 HPF and/or 3-20% Ki-67 index iii.If the mitotic ratio and Ki-67 index correspond to different grade, the higher grade is used to assign classification iv.Patients who have functioning NETs and have been on a stable dose of an SSA for a minimum of 2 months prior to the first dose of study treatment for control of their secr
Exclusion criteria
Exclusion criteria: 1. AEs due to previous antitumor therapy has not recovered to CTCAE =Grade 1, except alopecia and peripheral neurotoxicity with CTCAE =Grade 2 2. Part 2 patients with CRC (Cohort A), NETs (Cohort B), STS (Cohort E), and ATC (Cohort F): previous treatment with anti-PD-1, anti-PD-L1/L2 antibodies, anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) antibody, or any other antibody acting on T cell costimulatory or checkpoint pathway Note: Patients in the Part 1 and patients in Part 2 Cohorts C and D (SCLC and GC) may have received previous treatment with anti-PD-1, anti-PD-L1/L2 antibodies, CTLA-4 antibody, or any other antibody acting on T cell costimulatory or checkpoint pathway; 3. Previous treatment with surufatinib 4. Uncontrollable hypertension, defined as systolic blood pressure (BP) =140 mmHg and/or diastolic BP =90 mmHg 5. Gastrointestinal disease or condition that investigators suspect may affect drug absorption, including, but not limited to, 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 6. History or presence of a serious hemorrhage (>30 mL within 3 months), hemoptysis (>5 mL blood within 4 weeks), or life-threatening thromboembolic event within 6 months 7. Clinically significant cardiovascular disease, including but not limited to, acute myocardial infarction within 6 months prior to enrollment, severe/unstable angina pectoris or coronary artery bypass grafting, congestive heart failure according to the New York Heart Association classification =2, ventricular arrhythmias which need drug treatment, or left ventricular ejection fraction (LVEF) 2 weeks before the first dose of study treatment. b. Patients with a negative HCV antibody test at
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 To evaluate the safety and tolerability of surufatinib, thereby determining the recommended phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD) of surufatinib in combination with tislelizumab. Part 2 To evaluate the objective response rate (ORR) as assessed by the investigator in patients with advanced solid tumors when treated with surufatinib in combination with tislelizumab according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1;Secondary Objective: Part 1 • To evaluate the antitumor activity in patients with advanced solid tumors when treated with surufatinib in combination with tislelizumab according to RECIST v1.1 • To characterize the pharmacokinetics (PK) and immunogenicity of tislelizumab and surufatinib in combination Part 2 • To evaluate further anticancer effects of surufatinib in combination with tislelizumab • To characterize the safety and tolerability of surufatinib in combination with tislelizumab • To characterize the PK and immunogenicity of tislelizumab and surufatinib in combination;Primary end point(s): Part 1 Safety including dose-limiting toxicities (DLTs), treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events (AEs) leading to discontinuation, ECGs, clinical laboratory abnormalities, and vital signs Part 2 Objective Response Rate (ORR) at 12 weeks;Timepoint(s) of evaluation of this end point: Part 1: as stated in endpoint and for part 2: ORR at 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1 ORR, progression-free survival (PFS), disease control rate (DCR), clinical benefit rate (CBR), duration of response (DoR), time to response (TTR) • Concentrations of surufatinib in plasma and tislelizumab in serum • Incidence of antidrug antibodies (ADA) to tislelizumab Part 2 • PFS, DCR, CBR, DoR, TTR • OS: Cohorts A and F • Safety including TEAEs, SAEs, AEs leading to discontinuation, electrocardiograms (ECGs), clinical laboratory abnormalities, and study drug discontinuation due to AEs • Concentrations of surufatinib in plasma and tislelizumab in serum • Incidence of ADA to tislelizumab;Timepoint(s) of evaluation of this end point: Please refer to the study assessments in the protocol | — |
Countries
France, Italy, Spain, United States
Contacts
Public ContactNick Lawn
Hutchison MediPharma Limited
Outcome results
None listed