Tolerability and Pharmacokinetics of Toripalimab in Combination With Axitinib in Patients With Kidney Cancer and Melanoma

NCT03086174 | Unknown Phase 1 DMC

• 1 other identifier: Junshi-JS001-008
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase Ib, open, mono-center, dose-escalation, tolerability and pharmacokinetic study evaluating the Recombinant Humanized Anti-PD-1 mAb for Injection in combination with Axitinib in patients with advanced kidney cancer and melanoma who have failed in routine systemic treatment.

Conditions

Kidney Cancer Stage Iv; Advanced Melanoma

Keywords

anti-PD-1 monoclonal antibody; advanced; melanoma; kidney cancer

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Safety assessments including vital signs, laboratory tests, and adverse event monitoring

  3 years

Secondary Outcomes (17)

• PD-1 receptor occupancy of blood

  3 years

• Objective Response Rate (ORR) by irRC and RECIST 1.1

  3 years

• Duration of Response (DOR) by irRC and RECIST 1.1

  3 years

• Disease Control Rate (DCR) by irRC and RECIST 1.1

  3 years

• Time to response (TTR) by irRC and RECIST 1.1

  3 years

Other Outcomes (6)

• correlation analysis of PD-L1 expression of tumor and ORR

  3 years

• correlation analysis of PD-L1 expression of tumor and DOR

  3 years

• correlation analysis of PD-L1 expression of tumor and DCR

  3 years

Study Arms (1)

humanized anti-PD-1monoclonal antibody

EXPERIMENTAL

humanized anti-PD-1 monoclonal antibody is to be injected intravenously 1mg/kg or 3mg/kg Q2w PLUS axitinib 5 mg orally Q2w until disease progresses or unacceptable tolerability occurs

Biological: humanized anti-PD-1 monoclonal antibody Toripalimab

Interventions

humanized anti-PD-1 monoclonal antibody Toripalimab BIOLOGICAL

humanized anti-PD-1 monoclonal antibody Toripalimab is a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, which selectively interferes with the combination of PD-1 with its ligands, PD-L1 and PD-L2, resulting in the activation of lymphocytes and elimination of malignancy theoretically.

Also known as: JS001, TAB001

humanized anti-PD-1monoclonal antibody

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and Female aged between 18 and 75 years are eligible;
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
• At least received first-line treatment but appeared disease progression or intolerance, and a diagnosis of an advanced kidney Cancer and melanoma confirmed by pathology (Remark: Treatment intolerance including 1) The main organ function of the patient is evaluated by the doctor that can not be treated by the first-line standard;2) Patients received a first-line treatment with a 3/4 adverse reaction;3) Patients reject first-line treatment, etc)
• Providing with tumor specimen (for testing the expression of PD -L1 and the infiltrating lymphocytes);
• At least 1 measurable lesion (only 1 measurable lymph node lesion is excluded) (routine CT scan \>=20mm, spiral CT scan \>=10mm, no prior radiation to measurable lesions)
• Predicted survival \>=3 months;
• Brain or meningeal metastases must be disposed with surgery or radiation, and be stable clinically for at least 3 months (prior systemic steroids was allowed, but concurrent administration of systemic steroids with the study drug is excluded).
• Screening laboratory values must meet the following criteria（within past 14 days）:
• hemoglobin ≥ 9.0 g/dL; neutrophils ≥ 1500 cells/ µL; platelets ≥ 100 x 10\^3/ µL; total bilirubin ≤ 1.5 x upper limit of normal (ULN); aspartic transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis; serum creatinine ≤1╳ULN，creatinine clearance \>50ml/min (Cockcroft-Gault equation) INR, aPTT≤1.5 x ULN; Urine protein + 1 or less, if the urine protein \> 1 +, need to collect 24 hours urinary protein determination, the total amount should be 1 gram or less
• Without systemic steroids within past 4 weeks
• Males or female of childbearing potential must: agree to use using a reliable form of contraception (eg, oral contraceptives, intrauterine device, control sex desire, double barrier method of condom and spermicidal) during the treatment period and for at least 12 months after the last dose of study drug.
• Must have read, understood, and provided written informed consent voluntarily. Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

You may not qualify if:

• Prior treatment with anti-PD-1/PD-L1/PD-L2 antibody and Axitinib
• Hypersensitivity to recombinant humanized anti-PD-1 monoclonal Abm or its components
• Prior antitumor therapy (including corticosteroids and immunotherapy) or participation in other clinical trials within past 4 weeks, or have not recovered from toxicities since the last treatment;
• Pregnant or nursing;
• Positive tests for HIV, HCV, HBsAg or HBcAb with positive test for HBV DNA (\>500IU/ml);
• HBsAg or HBcAb with positive test for HBV DNA (\>500IU/ml)
• History with active tuberculosis;
• Associated with clinical symptoms or symptomatic treatment of pleural effusion or ascites;
• Patients with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, such as hypophysitis, pneumonia, colitis, hepatitis, nephritis, hyperthyroidism or hypothyroidism;
• Severe, uncontrolled medical condition that would affect patients' compliance or obscure the interpretation of toxicity determination or adverse events, including active severe infection, uncontrolled diabetes, angiocardiopathy (heart failure \> class II NYHA, heart block \>II grade, myocardial infarction, unstable arrhythmia or unstable angina within past 6 months, cerebral infarction within past 3 months) or pulmonary disease ( interstitial pneumonia, obstructive pulmonary disease or symptomatic bronchospasm).
• Evidence with active CNS disease;
• Prior treatment with bone marrow stimulating factors，such as CSF (colony stimulating factor), EPO (erythropoietin), within past 1 weeks;
• Prior live vaccine therapy within past 4 weeks;
• Received allogeneic hematopoietic stem cell transplantation or solid organ transplantation;
• Prior major surgery within past 4 weeks (diagnostic surgery excluded).

Sponsors & Collaborators

• Shanghai Junshi Bioscience Co., Ltd.: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Related Publications (3)

• Rini BI, Escudier B, Tomczak P, Kaprin A, Szczylik C, Hutson TE, Michaelson MD, Gorbunova VA, Gore ME, Rusakov IG, Negrier S, Ou YC, Castellano D, Lim HY, Uemura H, Tarazi J, Cella D, Chen C, Rosbrook B, Kim S, Motzer RJ. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011 Dec 3;378(9807):1931-9. doi: 10.1016/S0140-6736(11)61613-9. Epub 2011 Nov 4.

  PMID: 22056247 BACKGROUND

• Du Four S, Maenhout SK, De Pierre K, Renmans D, Niclou SP, Thielemans K, Neyns B, Aerts JL. Axitinib increases the infiltration of immune cells and reduces the suppressive capacity of monocytic MDSCs in an intracranial mouse melanoma model. Oncoimmunology. 2015 Jan 22;4(4):e998107. doi: 10.1080/2162402X.2014.998107. eCollection 2015 Apr.

  PMID: 26137411 BACKGROUND

• Li S, Wu X, Yan X, Zhou L, Chi Z, Si L, Cui C, Tang B, Mao L, Lian B, Wang X, Bai X, Dai J, Kong Y, Tang X, Feng H, Yao S, Flaherty KT, Guo J, Sheng X. Toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis. J Immunother Cancer. 2022 Feb;10(2):e004036. doi: 10.1136/jitc-2021-004036.

  PMID: 35193932 DERIVED

MeSH Terms

Conditions

Kidney Neoplasms; Melanoma

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Jun Guo

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

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: March 9, 2017
• First Posted: March 22, 2017
• Study Start: March 31, 2017
• Primary Completion: December 31, 2019
• Study Completion: December 1, 2020
• Last Updated: September 30, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)