Fruquitinib Combined With Camrelizumab in Non MSI-H/dMMR Refractory Colorectal Cancer

NCT04866862 | Unknown Phase 2

• 1 other identifier: KEEP-G 05
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Limited agents are optional after standard first and second line treatment for mCRC. Nowadays, cancer therapy has entered the era of immunotherapy. The approved cancer therapies include pembrolizumab and nivolumab, but only for MSI-H patients. 95% of non MSI-H / dMMR patients with advanced colorectal cancer can not benefit from them. Therefore, the use of PD-1 / PD-L1 monoclonal antibody in mCRC is greatly limited. Our previous research showed that anti-PD-1 combined with Fruquintinib can significantly inhibit the growth of CRC in MSS mice. At the same time, a retrospective clinical study showed that patients with MSS CRC can benefit from Sintilimab combined with Fruquintinib. Camrelizumab is PD-1 monoclonal antibody, which has been approved for a variety of tumors. The prospective clinical trial of Camrelizumab combined with Fruquintinib may bring new hope for the treatment of non MSI-H / dMMR patients with mCRC.This study is aimed to explore the efficacy, safety in advanced colorectal cancer failed to standard therapy in Chinese population.

Conditions

Colorectal Neoplasm

Keywords

colorectal cancer; non MSI-H/dMMR; Camrelizumab; Fruquintinib

Outcome Measures

Primary Outcomes (1)

• Objective response rate(ORR)

  The percentage of subjects with total number of Complete Response (CR) + total number of Partial Response (PR)

  up to 2 years

Secondary Outcomes (4)

• Progression-free Survival(PFS)

  From date of subjects until the date of first documented progression or death from any cause, whichever came first, assessed up to 24 months

• Overall Survival (OS)

  From assignment of the first subject until 32 death events observed, up to 2 years.

• Disease control rate (DCR)

  up to 2 years

• Tumor Mutation Burden (TMB)

  up to 2 years

Other Outcomes (1)

• immunocytes and cell factor

  up to 2 years

Study Arms (1)

Combination of Fruquintinib and Camrelizumab

EXPERIMENTAL

Fruquintinib 5mg d1-21+ Camrelizumab 200mg d1; Repeated every 4 weeks

Drug: Combination of Fruquintinib and Camrelizumab

Interventions

Combination of Fruquintinib and Camrelizumab DRUG

Fruquintinib 5mg d1-21+Camrelizumab 200 mg d1

Also known as: Fruquintinib 5mg d1-21+Camrelizumab 200 mg d1

Combination of Fruquintinib and Camrelizumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded.
• Subjects with non MSI-H / dMMR metastatic colorectal cancer(CRC) (Stage IV)
• Subjects must have failed at least two lines of prior treatment, which must include a fluoropyrimidine, oxaliplatin and irinotecan.
• Subjects must not have been treated with Fruquitinib or any anti-PD-1 inhibitors.
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1.is necessary.
• Adequate bone marrow, liver, cardiac and renal function as assessed by the laboratory required by protocol.
• Assigned informed consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
• Life expectancy of at least 3 months.
• Subjects must complete the treatment and follow-up on schedule according to the research plan.
• No brain metastasis, no spinal cord compression.
• Subjects agree to use blood samples for study analysis.
• Women of childbearing age must be negative in pregnancy test and willing to take effective contraceptive measures during the study period.

You may not qualify if:

• Subjects are severe malnutrition or need tube feeding.
• Radiotherapy or surgery has been performed within 30 days before treatment.
• Previous treatment with anti-PD-1 / PD-L1 inhibitor and / or fruquitinib.
• Other malignant tumors within 2 years and without cure (except for cured basal cell carcinoma of skin and carcinoma in situ of cervix);
• Subjects have active autoimmune system diseases、systemic hormone therapy or anti autoimmune drug therapy.
• Subjects with immunodeficiency or receiving systemic steroid therapy (prednisone \> 10 mg / day or other equivalent drugs) or other forms of immunosuppressive therapy 7 days before the first dose of combination therapy in this study;
• Subjects with active infection and still need systemic treatment 7 days before the first dose of therapy in this study.
• Subjects with uncontrollable systemic diabetes.
• Subjects with interstitial lung disease, non infectious pneumonia or pulmonary fibrosis;
• Subjects who have received allogeneic organ or stem cell transplantation in the past.
• Subjects allergic to the drugs or related components involved in this study.
• Are participating in other interventional clinical studies.
• The previous anti-tumor related adverses do not return to grade 1 in CTCAE before the first combination therapy.
• Subjects who have uncontrolled hypertension by drugs, that is, systolic blood pressure ≥ 140 mmHg and / or diastolic blood pressure ≥ 90 mmHg.
• Thrombotic or hemorrhagic tendency or history within 60 days before the first medication, regardless of the severity.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

the First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210029, China

RECRUITING

Related Publications (6)

• Jacquelot N, Yamazaki T, Roberti MP, Duong CPM, Andrews MC, Verlingue L, Ferrere G, Becharef S, Vetizou M, Daillere R, Messaoudene M, Enot DP, Stoll G, Ugel S, Marigo I, Foong Ngiow S, Marabelle A, Prevost-Blondel A, Gaudreau PO, Gopalakrishnan V, Eggermont AM, Opolon P, Klein C, Madonna G, Ascierto PA, Sucker A, Schadendorf D, Smyth MJ, Soria JC, Kroemer G, Bronte V, Wargo J, Zitvogel L. Sustained Type I interferon signaling as a mechanism of resistance to PD-1 blockade. Cell Res. 2019 Oct;29(10):846-861. doi: 10.1038/s41422-019-0224-x. Epub 2019 Sep 3.

  PMID: 31481761 RESULT

• Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, Stankevich E, Pons A, Salay TM, McMiller TL, Gilson MM, Wang C, Selby M, Taube JM, Anders R, Chen L, Korman AJ, Pardoll DM, Lowy I, Topalian SL. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010 Jul 1;28(19):3167-75. doi: 10.1200/JCO.2009.26.7609. Epub 2010 Jun 1.

  PMID: 20516446 RESULT

• Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017 Jul 28;357(6349):409-413. doi: 10.1126/science.aan6733. Epub 2017 Jun 8.

  PMID: 28596308 RESULT

• Xu J, Zhang Y, Jia R, Yue C, Chang L, Liu R, Zhang G, Zhao C, Zhang Y, Chen C, Wang Y, Yi X, Hu Z, Zou J, Wang Q. Anti-PD-1 Antibody SHR-1210 Combined with Apatinib for Advanced Hepatocellular Carcinoma, Gastric, or Esophagogastric Junction Cancer: An Open-label, Dose Escalation and Expansion Study. Clin Cancer Res. 2019 Jan 15;25(2):515-523. doi: 10.1158/1078-0432.CCR-18-2484. Epub 2018 Oct 22.

  PMID: 30348638 RESULT

• Mei Q, Zhang W, Liu Y, Yang Q, Rasko JEJ, Nie J, Liu J, Li X, Dong L, Chen M, Zhang Y, Shi L, Wu H, Han W. Camrelizumab Plus Gemcitabine, Vinorelbine, and Pegylated Liposomal Doxorubicin in Relapsed/Refractory Primary Mediastinal B-Cell Lymphoma: A Single-Arm, Open-Label, Phase II Trial. Clin Cancer Res. 2020 Sep 1;26(17):4521-4530. doi: 10.1158/1078-0432.CCR-20-0514. Epub 2020 Jun 4.

  PMID: 32499235 RESULT

• Shirley M. Fruquintinib: First Global Approval. Drugs. 2018 Nov;78(16):1757-1761. doi: 10.1007/s40265-018-0998-z.

  PMID: 30357594 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

camrelizumab; HMPL-013

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Rui Wang

  the first affilated hospital with Nanjing Medical University

  STUDY CHAIR

Central Study Contacts

Yanhong Gu, Dr

CONTACT

00862568306714; guluer@163.com

Xiaofeng Chen, Dr

CONTACT

008613585172066; xiaofengch198019@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2021
• First Posted: April 30, 2021
• Study Start: April 26, 2021
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2024
• Last Updated: July 25, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)