Lenvatinib in Combination With Camrelizumab as First-Line Therapy in Patients With Advanced HCC

NCT04443309 | Unknown Phase 1

• 1 other identifier: JS-2286
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single arm, open-label, non-randomized and single-center phase I/II clinical study, to evaluate the the safety, tolerance and efficacy of Lenvatinib plus Camrelizumab as first-line therapy in patients with advanced Hepatocellular Carcinoma.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients

  one year

Secondary Outcomes (8)

• Disease Control Rate (DCR)

  one year

• Progression-free Survival (PFS)

  one year

• Overall Survival (OS)

  one year

• Duration of Response (DOR)

  one year

• Clinical Benefit Rate (CBR)

  two years

Other Outcomes (1)

• Biomarker

  two years

Study Arms (1)

Lenvatinib plus Camrelizumab

EXPERIMENTAL

Camrelizumab (Jiangsu HengRui Medicine Co., Ltd.) is a recombinant anti-human PD-1 IgG4 monoclonal antibody. Lenvatinib is a novel angiogenesis inhibitor which targets multiple tyrosine kinases， including vascular endothelial growth factor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor β, RET and KIT.

Drug: Camrelizumab; Drug: Lenvatinib

Interventions

Camrelizumab DRUG

Camrelizumab 200mg,iv,d1,q2w

Also known as: SHR-1210

Lenvatinib plus Camrelizumab

Lenvatinib DRUG

Lenvatinib 8mg (\<60kg) or 12mg (≥60kg),po,d2,qd

Also known as: LENVIMA,E7080

Lenvatinib plus Camrelizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol;
• Males or females, age ≥ 18 years at the time of informed consent;
• Imaging (by AASLD or Standard for the diagnosis and treatment of primary liver cancer 2017 in China) or histopathologically or cytologically confirmed advanced HCC;
• BCLC stage B or C, and not suitable for surgical or local therapy, or has progressed following surgical and/or local therapy;
• No previous systematic treatment for HCC;
• Have at least one measurable lesion (in accordance with RECIST v1.1); the measurable lesion has a long diameter ≥ 10 mm or lymphadenopathy has a short diameter ≥ 15 mm in spiral CT scan;
• ECOG-PS score 0 or 1
• Child-Pugh Class: Grade A
• Life Expectancy of at least 3 months
• Subjects with HBV infection: HBV DNA\<2000 IU/ml or \<10\^4 copy/mL, and have received anti-HBV therapy for at least 14 days prior to enrollment in the study, subjects with HCV-RNA(+) must receive antiviral therapy;
• Hematology and organ functions are sufficient based on the following laboratory results within 14 days prior to the treatment of this study:
• Whole blood cell examination (no blood transfusion within 14 days, no G-CSF use and no drugs use): WBC ≥ 3.0×10\^9/L, HB ≥ 85 g/L; Neutrophils ≥ 1.5×10\^9/L; PLT≥75×10\^9/L; Biochemical examination (no ALB infused within 14 days): ALB ≥ 29 g/L; ALP and ALT and AST \< 5×ULN; TBIL≤3×ULN; Adequate renal function: Cr≤1.5×ULN, or CCr\>50mL/min; Female: CrCl = ((140- year) x weight (kg) x 0.85)/72x Cr (mg/dL) Male: CrCl = ((140- year) x weight (kg) x 1.00)/72xCr (mg/dL)
• Agree to abstain from sex (avoid heterosexual intercourse) or use contraceptive methods with an annual contraceptive failure rate of less than 1% during treatment and for at least 6 months after the last administration.

You may not qualify if:

• Hepatocellular carcinoma patients with any of the following:
• Suitable for radical surgery; without an assessment lesion after radical surgery; liver transplantation history or ready for liver transplantation;
• History of hepatic encephalopathy;
• Known hepatocholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and lamellar cell carcinoma;
• Pregnant women (positive pregnancy test before taking medicine) or lactating women;
• Known history of serious allergy to any monoclonal antibody or targeted anti-angiogenic drug (or any excipient);
• Received any topical treatment within 4 weeks prior to the study, including but not limited to surgery, radiotherapy, hepatic artery embolization, TACE, hepatic artery perfusion, radiofrequency ablation, cryoablation or percutaneous ethanol injection;
• Previous or existing CTCAE 5.0 standard grade 3 or above gastrointestinal fistula or non-gastrointestinal fistula (such as skin);
• Factors to affect oral administration and absorption (such as inability to swallow, chronic diarrhea and intestinal obstruction);
• Ascites with clinical symptoms (i.e. ascites with Child-Pugh rating \> 2) or cancerous ascites require therapeutic abdominal puncture or drainage. Or uncontrolled malignant ascites (ascites that researchers believe diuretics or puncture cannot control);
• Major surgical operations (except biopsy) were performed within 4 weeks prior to the first study of drug therapy or the surgical incision was not completely healed; Minor surgery (i.e. simple resection, biopsy, etc.) was performed within 7 days before the first round of research intervention.
• Cardiovascular and cerebrovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe/unstable angina pectoris, cerebrovascular accident or transient ischemic attack, congestive heart failure occurred within 6 months prior to admission (New York Heart Association Grade ≥2, see Appendix 4); Arrhythmia requiring antiarrhythmic drugs (except β receptor blocker or digoxin); Repeated ECG detection QTcF interval\>480 milliseconds (ms).
• Hepatic and renal insufficiency, such as jaundice, ascites, and/or bilirubin\>3×ULN, creatinine ratio\>3.5g/24h, or renal failure requiring blood or peritoneal dialysis, etc. And/or urine routine showed proteinuria ≥++or confirmed 24-hour proteinuria\>1.0g.
• Persistent\>2 grade (CTC-AE5.0) infection.
• History of thromboembolism (including stroke and/or transient ischemic attack) in the past 6 months.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Jiangsu HengRui Medicine Co., Ltd.: collaborator

Study Sites (1)

Chinese Academy of Medical Sciences & Peking Union Medical College Hospital

Beijing, Please Select, 100730, China

RECRUITING

Related Publications (12)

• Villanueva A. Hepatocellular Carcinoma. N Engl J Med. 2019 Apr 11;380(15):1450-1462. doi: 10.1056/NEJMra1713263. No abstract available.

  PMID: 30970190 BACKGROUND

• Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015 Mar 1;136(5):E359-86. doi: 10.1002/ijc.29210. Epub 2014 Oct 9.

  PMID: 25220842 BACKGROUND

• Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012 Mar 31;379(9822):1245-55. doi: 10.1016/S0140-6736(11)61347-0. Epub 2012 Feb 20.

  PMID: 22353262 BACKGROUND

• Llovet JM, Montal R, Villanueva A. Randomized trials and endpoints in advanced HCC: Role of PFS as a surrogate of survival. J Hepatol. 2019 Jun;70(6):1262-1277. doi: 10.1016/j.jhep.2019.01.028. Epub 2019 Mar 31.

  PMID: 30943423 BACKGROUND

• Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. doi: 10.1056/NEJMoa0708857.

  PMID: 18650514 BACKGROUND

• Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009 Jan;10(1):25-34. doi: 10.1016/S1470-2045(08)70285-7. Epub 2008 Dec 16.

  PMID: 19095497 BACKGROUND

• Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.

  PMID: 29433850 BACKGROUND

• 8. Qin S OX, Bai Y, Cheng Y, Chen Z, Ren Z, Song T, Dutcus C, Saito K, Tamai T, Yau TCC, Rau K-M, Cheng A-L, Han G. Subgroup analysis of Chinese patients in a phase 3 study of lenvatinib vs sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma. Hepatol Int 2019;13:S170.

  BACKGROUND

• Boussiotis VA. Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway. N Engl J Med. 2016 Nov 3;375(18):1767-1778. doi: 10.1056/NEJMra1514296. No abstract available.

  PMID: 27806234 BACKGROUND

• Ma W, Gilligan BM, Yuan J, Li T. Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy. J Hematol Oncol. 2016 May 27;9(1):47. doi: 10.1186/s13045-016-0277-y.

  PMID: 27234522 BACKGROUND

• Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.

  PMID: 32402160 BACKGROUND

• Qin S, Ren Z, Meng Z, Chen Z, Chai X, Xiong J, Bai Y, Yang L, Zhu H, Fang W, Lin X, Chen X, Li E, Wang L, Chen C, Zou J. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Lancet Oncol. 2020 Apr;21(4):571-580. doi: 10.1016/S1470-2045(20)30011-5. Epub 2020 Feb 26.

  PMID: 32112738 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

camrelizumab; lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Haitao Zhao, MD

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaobo Yang

CONTACT

010-69156043; yangxulcyx@163.com

Xiao-Bo Yang

CONTACT

010-69156043; yangxiaobo67@pumch.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2020
• First Posted: June 23, 2020
• Study Start: September 11, 2020
• Primary Completion: August 1, 2024
• Study Completion: August 1, 2024
• Last Updated: March 29, 2023

Record last verified: 2023-01

Locations

CN (1)