Clinical trial NCT03731390: GR1405 Injection in Patients With Advanced Solid Tumor or Lymphoma
Official title: A Phase I Clinical Study for Evaluating the Safety, Pharmacokinetics, and Preliminary Efficacy of Repeated Doses, Dose Escalation of GR1405 Injection in Patients With Advanced Solid Tumor or Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Tumor, Solid
Lymphoma
Keywords: programmed death ligand-1 (PD-L1)
Lead sponsor: ChineseAMS
Sponsor class: UNKNOWN
First posted: 2018-11-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase I clinical study for evaluating the safety, pharmacokinetics, and preliminary efficacy of repeated doses, dose escalation of GR1405 injection in patients with advanced solid tumor or lymphoma

Detailed description: To evaluate the tolerability, safety, pharmacokinetics, and preliminary efficacy of GR1405 injection monotherapy in an open, non-controlled, escalating trial design in patients with advanced solid tumors or lymphomas. Four dose levels (3 mg/kg, 10 mg/kg, 20 mg/kg, and 30 mg/kg) were evaluated at this stage.

Eligibility criteria: Inclusion Criteria:

1. Patients with local advanced, recurrent or metastatic solid tumors confirmed by cytology or histology Lymphoma patients with pathological confirmation, and the above pat reients failed to standard treatment failure or had no standard treatment;
2. Aged 18 to 75 years men and women;
3. At least one measurable or evaluable lesion according to Response Evaluation Criteria in Solid Tumors v1.1(RECIST v1.1 )(solid tumor) or Lugano 2014 criteria (lymphoma);
4. Eastern Cooperative Oncology Group(ECOG)≤ 1
5. Female or male subjects of reproductive age and their mate are willing to take effective contraceptive measures for the entire treatment period and 6 months after the treatment;
6. With sufficient organ and bone marrow function;
7. At least 4 weeks after the last anti-tumor treatment before the first administration;
8. The patient or his legal representative signs a written informed consent.

Exclusion Criteria:

1. Have experienced any National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) v4.03 or greater than 3 grade irAE during previous immunotherapy treatment;
2. Has received any anti-PD-1(programmed death 1) or anti-PD-L1 antibody treatment;
3. Subjects with other malignant tumors previously or concurrently ;
4. Female patients with pregnancy or lactation;
5. Women/men who have fertility refusal to adopt contraception during the trial period;
6. Subjects with serious disease or complications, such as gastrointestinal bleeding, intestinal obstruction, intestinal paralysis, interstitial pneumonia, pulmonary fibrosis, renal failure, glaucoma, uncontrolled diabetes (CTCAE= 4.03: fasting blood glucose level ≥ 2), and with active infection;
7. Had history of acute myocardial infarction, unstable angina pectoris, stroke or transient ischemic attack 6 months before the screening ,grade 2 or above congestive heart failure devised by the New York Heart Association (NYHA);
8. Subjects with symptomatic brain metastases or mental disorders;
9. Subjects with abnormal levels of serum calcium, magnesium, potassium and have clinical significance;
10. Subjects with history of immunodeficiency, including human immunodeficiency virus(HIV)-positive, suffering from other acquired, congenital immunodeficiency disease, or history of organ transplantation;
11. Subjects with active hepatitis B (HBsAg and/or HBcAb positive, and HBV DNA titer in peripheral blood was greater than 1 x 103 IU/ml), and/or hepatitis C;
12. Subjects who have alcohol addiction and/or drug abuse;
13. Subjects with bleeding or coagulation dysfunction in the past 3 months (Prothrombin time(PT)\>1.5×upper limit of normal(ULN); activated partial thromboplastin time(APTT)\>1.5×ULN; thrombin time(TT)\>1.5×ULN);
14. Subjects with allergic constitution or allergic to known components of the drug;
15. Those who received other clinical trial drug therapy within 1 month before the first administration;
16. Receive a live attenuated vaccine within 4 weeks prior to the first dose of study treatment or during the study period;
17. Other subjects judged by the investigator to be ineligible for enrollment in the study.

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: 2 weeks
measure: Adverse Events
timeFrame: Approximately 3 years
Secondary outcomes:
measure: maximum concentration (Cmax)
timeFrame: Approximately 2 years
measure: Duration of response (DOR)
timeFrame: Approximately 3 years
measure: Objective Response Rate(ORR)
timeFrame: Approximately 3 years
measure: Progression free survival(PFS)
timeFrame: Approximately 3 years
measure: Immunogenicity
timeFrame: Approximately 3 years
measure: Recommended dose for Phase II trial(RP2D)
timeFrame: Approximately 3 years
measure: AUC0-t
timeFrame: Approximately 2 years
measure: AUC0-∞
timeFrame: Approximately 2 years
measure: AUCss
timeFrame: Approximately 2 years
measure: T max
timeFrame: Approximately 2 years
measure: t 1/2
timeFrame: Approximately 2 years
measure: apparent volume of distribution (Vz)
timeFrame: Approximately 2 years
measure: clearance(CL)
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Institute/Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Study officials:
affiliation: Chinese Academy of Medical Sciences
name: yuankai Shi, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: El-Khoueiry AB, Sangro B, Yau T, Crocenzi TS, Kudo M, Hsu C, Kim TY, Choo SP, Trojan J, Welling TH Rd, Meyer T, Kang YK, Yeo W, Chopra A, Anderson J, Dela Cruz C, Lang L, Neely J, Tang H, Dastani HB, Melero I. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017 Jun 24;389(10088):2492-2502. doi: 10.1016/S0140-6736(17)31046-2. Epub 2017 Apr 20.
citation: Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, Loriot Y, Necchi A, Hoffman-Censits J, Perez-Gracia JL, Dawson NA, van der Heijden MS, Dreicer R, Srinivas S, Retz MM, Joseph RW, Drakaki A, Vaishampayan UN, Sridhar SS, Quinn DI, Duran I, Shaffer DR, Eigl BJ, Grivas PD, Yu EY, Li S, Kadel EE 3rd, Boyd Z, Bourgon R, Hegde PS, Mariathasan S, Thastrom A, Abidoye OO, Fine GD, Bajorin DF; IMvigor210 Study Group. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017 Jan 7;389(10064):67-76. doi: 10.1016/S0140-6736(16)32455-2. Epub 2016 Dec 8.
citation: Schachter J, Ribas A, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank C, Petrella TM, Hamid O, Zhou H, Ebbinghaus S, Ibrahim N, Robert C. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet. 2017 Oct 21;390(10105):1853-1862. doi: 10.1016/S0140-6736(17)31601-X. Epub 2017 Aug 16.