First in Human Study of IBI308 in Chinese Subjects With Advanced Solid Tumors

NCT02937116 | Completed Phase 1 Results

• 1 other identifier: CIBI308A101
• Study Type: interventional
• Target: 233
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety, tolerability and efficacy of IBI308 monotherapy or in combination with chemotherapy in patients with certain types of advanced solid tumors. Another purpose is to determine the pharmacokinetics, pharmacodynamics and immunogenicity of IBI308.

Conditions

Cancer, Solid Tumor

Outcome Measures

Primary Outcomes (3)

• Number of Participants Experiencing Dose-limiting Toxicities (DLTs)

  Up to 28 days in Cycle 1

• Number of All Study Participants Who Demonstrate a Tumor Response

  Through out the study (up to 2 years)

• Objective Response Rate (ORR) According to RECIST 1.1 as Assessed by Independent Review Committee by Investigator

  ORR was defined as the percentage of participants in the analysis population who had achieved BOR of CR or PR according to RECIST 1.1.

  Through out the study (up to 2 years)

Secondary Outcomes (10)

• PFS According to RECIST 1.1 as Assessed by Investigator

  Through out the study (up to 2 years)

• DOR According to RECIST 1.1 as Assessed by Investigator

  Through out the study (up to 2 years)

• TTR According to RECIST 1.1 as Assessed by Investigator

  Through out the study (up to 2 years)

• OS for Participants

  Through out the study

• Area Under the Concentration-time Curve From Zero Time (Predose) to the Time of the Last Measurable Concentration (AUC0-t)

  Cycle 1: pre-dose, post-dose at 0, 1, and 6 hours, and Days 2, 3, 8, 15, and 22, and 29

Study Arms (9)

Phase 1a

EXPERIMENTAL

Participants will receive IBI308 1mg/kg, 3mg/kg or 10mg/kg intravenous every 2 weeks, or 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity. Drug: IBI308

Drug: IBI308

Phase 1b Cohort A

EXPERIMENTAL

Participants will receive IBI308 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. Drug: IBI308

Drug: IBI308

Phase 1b Cohort B

EXPERIMENTAL

Participants will receive IBI308 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. Drug: IBI308

Drug: IBI308

Phase 1b Cohort C

EXPERIMENTAL

Participants will receive IBI308 200mg intravenous every 3 weeks and will be continued until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. Drug: IBI308

Drug: IBI308

Phase 1b Cohort D

EXPERIMENTAL

Participants will receive IBI308 200mg in combination with cisplatin 75mg/m2 and pemetrexed 500mg/m2 intravenously every 3 weeks for upto 4 cycles, and those who haven't progressed will receive maintenance treatment of IBI308 200mg in combination with pemetrexed 500mg/m2 intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. Drug: IBI308/Cisplatinum/Pemetrexed

Drug: IBI308\Cisplatinum\Pemetrexed

Phase 1b Cohort E

EXPERIMENTAL

Participants will receive IBI308 200mg and cisplatin 75mg/m2 intravenously every 3 weeks in combination with gemcitabine 1250mg/m2 intravenously day 1 and 8 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. Drug: IBI308\\gemcitabine\\cisplatin

Drug: IBI308\cisplatin\gemcitabine

Phase 1b Cohort F

EXPERIMENTAL

Participants will receive IBI308 200mg and oxaliplatin 130mg/m2 intravenously every 3 weeks in combination with capecitabine 1000mg/m2 orally day 1 to 14 of every 3 weeks for upto 6 cycles, and those those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. Drug: IBI308\\oxaliplatin\\capecitabine

Drug: IBI308\oxaliplatin\capecitabine

Phase 1b Cohort G

EXPERIMENTAL

Participants will receive IBI308 200mg in combination with cisplatin 75mg/m2 intravenously and etoposide 100mg/m2 intravenously day 1 to 3 of every 3 weeks for upto 6 cycles. Those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. Drug: IBI308\\etoposide\\cisplatin

Drug: IBI308\etoposide\cisplatin

Phase 1b Cohort H

EXPERIMENTAL

Participants will receive IBI308 200mg in combination with irinotecan 125mg/m2 intravenously day 1and 8 and 5-FU 1000mg/m2 intravenously day 1 to 3 of every 3 weeks for upto 6 cycles.Those who haven't progressed will receive maintenance treatment of IBI308 200mg intravenously every 3 weeks until disease progression or unacceptable toxicity or withdrawal of informed consent or up to 24 months of treatment. Drug: IBI308\\irinotecan\\5-FU

Drug: IBI308\irinotecan\5-FU

Interventions

IBI308 DRUG

Phase 1a; Phase 1b Cohort A; Phase 1b Cohort B; Phase 1b Cohort C

IBI308\Cisplatinum\Pemetrexed DRUG

Phase 1b Cohort D

IBI308\cisplatin\gemcitabine DRUG

Phase 1b Cohort E

IBI308\oxaliplatin\capecitabine DRUG

Phase 1b Cohort F

IBI308\etoposide\cisplatin DRUG

Phase 1b Cohort G

IBI308\irinotecan\5-FU DRUG

Phase 1b Cohort H

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1
• Adequate bone marrow, liver, and renal function defined as: 1) Absolute neutrophil count \>= 1.5\* 10\^9 cells/litre (L); 2) Platelets \>=100 x 10\^9 cells/L; 3) Hemoglobin \>= 9 gram/deciliter (g/dL); 4) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<= 2.5 \* upper limit of normal (ULN) for participants without hepatic cell cancer and hepatic metastasis, ALT and AST \<= 5 \* ULN for participants with hepatic cell cancer or hepatic metastasis; 5) Total bilirubin (TBIL) \< 1.5 \* ULN for participants without hepatic cell cancer, hepatic metastasis and confirmed/suspicious Gilbert syndrome, TBIL \< 3 \* ULN for participants with hepatic cell cancer, hepatic metastasis or confirmed/suspicious Gilbert syndrome; 6) Creatinine determined by serum creatinine levels \<=1.5 \* ULN or a calculated creatinine clearance of \>= 50 mL/min/1.73 m\^2; 7) urine protein -\~+, 24 hour urine \< 1 gram for participants with urine protein ++ or above; 8) activated partial thromboplastin time and international normalized ratio \<= 1.5 \* ULN; 9) thyroid stimulating hormone and free thyroxine 4 within normal range
• Tumor type
• Phase 1a: advanced solid tumors after failure of standard therapy
• Phase 1b Cohort A: cytologically or histologically confirmed advanced melanoma
• Phase 1b Cohort B: cytologically or histologically confirmed advanced malignancies of the digestive system after failure of at least 1 line of standard therapy
• Phase 1b Cohort C: cytologically or histologically confirmed advanced NSCLC without known epithelial growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement after failure of 1st line standard therapy
• Phase 1b Cohort D: treatment naive cytologically or histologically confirmed inoperable locally advanced (stage IIIB) or advanced (stage IV) nsNSCLC without known EGFR mutation and ALK rearrangement, participants with disease recurrence or progression within 6 months after completion of prior platinum doublet-based chemotherapy regimen as neoadjuvant or adjuvant therapy are not eligible
• Phase 1b Cohort E: Cytologically or histologically confirmed, treatment naïve locally advanced, recurrent or metastatic squamous NSCLC without known EGFR mutation and ALK rearrangement. Participants with Stage IIIB NSCLC who progressed within 6 months after completion of platinum-based chemotherapy are not eligible.
• Phase 1b Cohort F: Histologically confirmed locally advanced, recurrent or metastatic gastric or esophagogastric junction adenocarcinoma without known HER2 amplification.
• Phase 1b Cohort G: Cytologically or histologically confirmed, treatment naïve locally advanced, recurrent or metastatic high grade(G3) neuroendocrine tumor with Ki-67\>20%.
• Phase 1b Cohort H: Cytologically or histologically confirmed advanced high grade(G3) neuroendocrine tumor with Ki-67\>20% after failure of first line standard therapy. Participants progressed within 6 months after completion of adjuvant or neoadjuvant chemotherapy are eligible.
• At least 1 measurable site of disease per RECIST v1.1

You may not qualify if:

• Prior treatment of any antibody of PD-1 or PD-L1
• Prior treatment of ipilimumab, unless all the following requirements are met:
• Full resolution of ipilimumab related adverse effects (including immune related adverse effects) and no treatment for these adverse events (AEs) for at least 4 weeks prior to the time of enrollment
• Minimum of 12 weeks from the first dose of ipilimumab and \>6 weeks from the last dose
• No history of severe immune related adverse effects from ipilimumab (CTCAE Grade 4; CTCAE Grade 3 requiring treatment \>4 weeks)
• Unequivocal PD following a dose of ipilimumab
• HIV infection
• Active HBV or HCV infection
• Uncontrolled complication including but not limited to :
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias or congestive heart failure
• History of stroke, myocardial infarction or intracranial hemorrhage within 6 months prior to the enrolment
• History or risk of autoimmune disease
• Known interstitial lung disease

Sponsors & Collaborators

• Innovent Biologics (Suzhou) Co. Ltd.: lead

Study Sites (1)

The fifth medical center of the PLA general hospital

Beijing, China

Location

Related Publications (6)

• Jiang H, Zheng Y, Qian J, Mao C, Xu X, Li N, Xiao C, Wang H, Teng L, Zhou H, Wang S, Zhu D, Peng B, Shen L, Xu N. Safety and efficacy of sintilimab combined with oxaliplatin/capecitabine as first-line treatment in patients with locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma in a phase Ib clinical trial. BMC Cancer. 2020 Aug 14;20(1):760. doi: 10.1186/s12885-020-07251-z.

  PMID: 32795349 RESULT

• Jiang H, Zheng Y, Qian J, Mao C, Xu X, Li N, Xiao C, Wang H, Teng L, Zhou H, Wang S, Zhu D, Sun T, Yu Y, Guo W, Xu N. Efficacy and safety of sintilimab in combination with chemotherapy in previously untreated advanced or metastatic nonsquamous or squamous NSCLC: two cohorts of an open-label, phase 1b study. Cancer Immunol Immunother. 2021 Mar;70(3):857-868. doi: 10.1007/s00262-020-02738-x. Epub 2020 Oct 17.

  PMID: 33070260 RESULT

• Wei J, Lu X, Liu Q, Fu Y, Liu S, Li L, Liu F, Fan X, Yang J, Yang Y, Zhao Y, Guan W, Liu B. Efficacy and Safety of Sintilimab in Combination with Concurrent Chemoradiotherapy for Locally Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (SHARED): Study Protocol of a Prospective, Multi-Center, Single-Arm Phase 2 Trial. Cancer Manag Res. 2022 Jun 17;14:2007-2015. doi: 10.2147/CMAR.S355687. eCollection 2022.

  PMID: 35747712 DERIVED

• Jia R, Li Y, Xu N, Jiang HP, Zhao CH, Liu RR, Shi Y, Zhang YY, Wang SY, Zhou H, Xu JM. Sintilimab in Patients with Previously Treated Metastatic Neuroendocrine Neoplasms. Oncologist. 2022 Aug 5;27(8):e625-e632. doi: 10.1093/oncolo/oyac097.

  PMID: 35647908 DERIVED

• Jiang H, Li N, Wang H, Chen Z, Zheng Y, Qian J, Mao C, Xu X, Xiao C, Zhang X, Zhou H, Wang S, Chen W, Yin X, Sun J, Peng B, Teng L, Xu N. Assessment of TMB, PD-L1, and lymphocyte to monocyte ratio as predictive potential in a phase Ib study of sintilimab in patients with advanced solid tumors. Am J Cancer Res. 2021 Sep 15;11(9):4259-4276. eCollection 2021.

  PMID: 34659886 DERIVED

• Zhang J, Wu L, Liu J, Lin M. A metastatic intrahepatic cholangiocarcinoma treated with programmed cell death 1 inhibitor: a case report and literature review. Immunotherapy. 2020 Jun;12(8):555-561. doi: 10.2217/imt-2019-0100. Epub 2020 May 6.

  PMID: 32372672 DERIVED

Related Links

• Abstract for Cohort E on Jtho.2018

MeSH Terms

Conditions

Neoplasms

Interventions

sintilimab

Results Point of Contact

• Title: Yi Bo
• Organization: Innovent Biologics (Suzhou) Co., Ltd. (seal)

jessica.yi@innoventbio.com

+8613382419112

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2016
• First Posted: October 18, 2016
• Study Start: October 19, 2016
• Primary Completion: September 30, 2020
• Study Completion: September 30, 2020
• Last Updated: October 14, 2022
• Results First Posted: February 21, 2021

Record last verified: 2022-09

Locations

CN (1)