Clinical trial NCT05327231: IN10018 Monotherapy or in Combination With Docetaxel in Gastric or GEJ Adenocarcinoma
Official title: A Phase I, Open-label Clinical Trial to Evaluate Safety, Tolerability, Antitumor Activities and Pharmacokinetics of IN10018 as Mono or Combination Therapy in Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gastric Cancer
Lead sponsor: InxMed (Shanghai) Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-04-14
Enrollment: 33
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, multi-center clinical trial to evaluate the safety, tolerability, antitumor activities and pharmacokinetics of IN10018 as monotherapy or in combination with docetaxel in previously-treated locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Detailed description: Eligibility patients will be enrolled into the study and assigned to treatment groups: 1) IN10018 monotherapy group, and 2) IN10018+Docetaxel combination group. This study contains 2 parts of dose escalation and dose expansion for each treatment group. The monotherapy group will enroll patients failed to respond to standard therapy or standard or curative therapy does not exist or is not tolerable, and explore IN10018 monotherapy RP2D with the starting dose of IN10018 100mg QD per 3+3 design. The combination group will enroll patients who have disease progression within 3 months after at least first-line therapy, and explore IN10018+docetaxel RP2D with the starting dose of IN10018 100mg QD + docetaxel 75mg/m2 per 3+3 design. The dose expansion part will start after attaining the RP2D of IN10018 monotherapy and IN10018+docetaxel combination therapy.

Eligibility criteria: Inclusion Criteria:

* 1.Has histologically or cytologically confirmed diagnosis of locally advanced and/or metastatic gastric or GEJ adenocarcinoma.

  * For monotherapy, participants need to be failed to respond to standard therapy or standard or curative therapy does not exist or is not tolerable.
  * For combination therapy, participants need to have disease progression within 3 months after at least first-line therapy.
* 2.Has at least one measurable tumor lesion per RECIST 1.1.
* 3.Has an ECOG performance status of 0 or 1.
* 4.Estimated life expectancy is more than 3 months.
* 5.Adequate organ and bone marrow functions.
* 6.Has been fully informed and provided written informed consent for the study

Exclusion Criteria:

* 1.Has other histological types other than adenocarcinoma.
* 2.For participants with HER2/neu positive tumors or have an unknown tumor status, need to match the following:

  * If HER2/neu positive, participant must have documentation of disease progression on trastuzumab or other anti-HER2/neu therapy.
  * Participants with unknown status must have their HER2/neu status determined locally. If HER2/neu-negative, the participant will be eligible. If HER2/neu-positive, the participant must have documentation of disease progression on trastuzumab or other anti-HER2/neu therapy.
* 3.Has had disease progression after docetaxel/paclitaxel containing treatment (combination therapy only).
* 4.Has received prior systemic therapies (i.e. chemotherapy, biotherapy, endocrinotherapy, and immunotherapy) within 4 weeks prior to start of study treatment.
* 5.Has received prior radiotherapy within 2 weeks prior to start of study treatment.
* 6.Has severe allergy or hypersensitivity to IN10018 and/or docetaxel, or any components used in their preparation or has contraindication for taxane therapy. For participants in monotherapy group, only restriction to IN10018 applies.
* 7.Has severe renal disease or impaired renal function.
* 8.Has an active infection requiring systemic therapy within 2 weeks prior to start of study treatment.
* 9.Has a history or current evidence of interstitial lung disease.

Primary outcomes:
measure: Safety and tolerability in combination group
timeFrame: up to 24 months
measure: DLTs in combination group
timeFrame: 21 days
measure: Phase II dose of IN10018 in combination with Docetaxel
timeFrame: up to 24 months
Secondary outcomes:
measure: Safety and tolerability in IN10018 monotherapy group
timeFrame: up to 24 months
measure: DLTs in IN10018 monotherapy group
timeFrame: up to 24 months
measure: Objective response rate (ORR) per RECIST v1.1
timeFrame: up to 24 months
measure: Duration of objective response (DOR) per RECIST v1.1.
timeFrame: up to 24 months
measure: Disease Control Rate (DCR) per RECIST v1.1.
timeFrame: up to 24 months
measure: Progression-free survival (PFS) per RECIST v1.1.
timeFrame: up to 24 months
measure: Overall survival (OS).
timeFrame: up to 30 months
measure: Pharmacokinetics (PK):AUC
timeFrame: up to 24 months
measure: Pharmacokinetics (PK):Cmax
timeFrame: up to 24 months
measure: PK:Tmax
timeFrame: up to 24 months
measure: PK:Ctrough
timeFrame: up to 24 months
measure: PK:t1/2
timeFrame: up to 24 months
measure: PK:CL/F
timeFrame: up to 24 months
measure: PK:Vd/F
timeFrame: up to 24 months
Other outcomes:
Locations:
city: Anyang
country: China
facility: Anyang Tumor Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Nanjing
country: China
facility: The Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
city: Xi'an
country: China
facility: The First Affiliated Hospital of XI 'AN Jiaotong University
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
Study officials:
affiliation: Shanghai East Hospital
name: Jin Li, Doctor
role: PRINCIPAL_INVESTIGATOR
References: