Treatment of Patients With Advanced Solid Tumors With Oral Agent ORIN1001 and in Combination With Standard of Care.

NCT05154201 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: ORIN1001-C1
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 13

Brief Summary

Dose escalation of ORIN1001 in patients with advanced solid tumors. Dose escalation of ORIN1001 in combination with standard of care in patients with esophageal carcinoma, metastatic breast cancer, hepatocellular carcinoma, metastatic prostate cancer, pancreatic cancer, ovarian cancer and non-small cell lung cancer. Dose expansion of ORIN1001 as a single agent or in combination with standard of care in patients with advanced solid tumors.

Conditions

Effect of Drug

Keywords

anti-tumor

Outcome Measures

Primary Outcomes (12)

• Assessment of tolerability

  Whole blood sample collected for Hematology evaluation

  Change from baseline through completion of study

• Assessment of tolerability

  whole blood sample collected for Serum clinical chemistry

  Change from baseline through completion of study

• Assessment of tolerability

  Urine sample collected for Urinalysis

  Change from baseline through completion of study

• Assessment of tolerability

  Electrocardiogram (ECG) - A 12-lead ECG will evaluate electrical cardiac intervals P, QRS, and QT.

  Change from baseline through completion of study

• Assessment of tolerability

  Ultrasound Cardiogram (MUGA) will evaluate a cardiac physiologic parameter.

  Change from baseline through completion of study

• Assessment of tolerability

  ECOG performance score (Eastern Cooperative Oncology Group) will be measured by clinician. ECOG scores range from 0 to 5. 0 is fully active and 5 is death.

  Evaluated during baseline or pre-intervention and during intervention.

• Assessment of tolerability

  Body weight in kilogram (kg) will be measured on a calibrated scale.

  Change from baseline through completion of study

• Pharmacokinetic Evaluation

  A blood sample will be collected to determine the concentration of ORIN1001 in plasma using analysis in a clinical lab.

  Collected on Day 1 and on Day 21 or Day 28. One cycle with single agent is 21 days and one cycle in combination with chemotherapy is 28 days.

• Assessment of tolerability

  Blood pressure, including systolic and diastolic measurements.

  Change from baseline through completion of study

• Assessment of tolerability

  Pulse rate

  Change from baseline through completion of study

• Assessment of tolerability

  Body temperature

  Change from baseline through completion of study

• Assessment of tolerability

  Respiration rate

  Change from baseline through completion of study

Secondary Outcomes (3)

• Assessment of Efficacy

  Change from baseline through completion of study

• Assessment of Tumor type

  Predose or baseline

• Biomarker evaluation

  Predose or baseline and once during intervention.

Study Arms (3)

Dose escalation of ORIN1001 as a single agent

EXPERIMENTAL

Single-agent dose escalation in Chinese patients with advanced solid tumors. Nine dose groups: 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 650 mg, 900 mg, 1200 mg, and 1500 mg orally in 21-day cycles. A total of 27-54 evaluable patients are expected to be enrolled. However, the dose in the escalation phase is not limited to these dose groups, and the number of enrolled patients is not limited to 27-54.

Drug: ORIN1001

Dose escalation of ORIN1001 in combination with Standard of Care

EXPERIMENTAL

ORIN1001 will be administered daily as a tablet in combination with standard of care. This arm of the study will be carried out in 8 different cancer indications, including advanced triple-negative breast cancer received ≥ 3 lines of treatment, postmenopausal ER+/HER2-advanced breast cancer received the 1 line of treatment, advanced hepatocellular carcinoma received 1/2 line of treatment, chemotherapy-naive castrate-resistant prostatic cancer, advanced pancreatic cancer received 1/2 line of treatment, platinum-resistant/refractory advanced ovarian cancer received ≥ 2 lines of treatment, non-small cell lung cancer received ≥ 2 lines of treatment, and esophageal cancer received ≥ 2 lines of treatment.

Drug: ORIN1001

Dose expansion of ORIN1001 as a single agent or in combination with Standard of Care

EXPERIMENTAL

After the recommended phase 2 dose of single-agent ORIN1001 is determined, a single-agent efficacy expansion study for advanced esophageal cancer, as well as a single-agent efficacy expansion study for advanced solid tumors with failure of standard treatments or no effective standard treatment. After the recommended phase 2 dose of the combination treatment is determined, the efficacy expansion study of the combination treatment will be conducted in the corresponding 8 different indications.

Drug: ORIN1001

Interventions

ORIN1001 DRUG

Dose escalation of ORIN1001 as a single agent or in combination with standard of care. Dose expansion of ORIN1001 as a single agent or in combination with standard of care.

Dose escalation of ORIN1001 as a single agent; Dose escalation of ORIN1001 in combination with Standard of Care; Dose expansion of ORIN1001 as a single agent or in combination with Standard of Care

Eligibility Criteria

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

You may qualify if:

• The patients must meet all of the following conditions:
• Male or female, ≥ 18 years of age.
• Provide evidence of disease progression or intolerable toxicity as confirmed by the investigator or documented in the medical history before enrollment;
• Adequate organ functions, including all the following functions: Adequate bone marrow reserve, defined as: Absolute neutrophil count (ANC) ≥ 1.0 × 109/L; lymphocytes count ≥ 0.5 × 109/L; platelet count ≥ 100 × 109/L; hemoglobin ≥ 90 g/L; liver function (except hepatocellular carcinoma cohort): Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN), ≤ 3.0 × ULN for patients with Gilbert syndrome; aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × ULN; ALP ≤ 2.5 × ULN; AST, ALT, ALP ≤ 5 × ULN for liver cancer patients or patients concomitantly with liver metastases; INR and APTT \< 1.5 × ULN (patients receiving anticoagulant therapy are required to maintain dose stability within the recent two weeks (liver cancer patients are not allowed to take anticoagulants simultaneously for patients); renal function: Creatinine \< 1.5 × ULN, or normal range of serum creatinine or creatinine clearance ≥ 50ml/min/1.73m2. Creatinine clearance is calculated using the Cockroft-Gault formula. Albumin ≥ 30 g/L.
• Known left ventricular ejection fraction (LVEF) \> 50%.
• Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
• Patients with at least one evaluable lesion (single-agent dose escalation period) and at least one measurable lesion (single-agent dose expansion and combination therapy dose-finding/expansion period) according to RECIST Version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 1.
• Able to understand and willing to sign an informed consent form prior to the initiation of any study procedures; patients have an expected survival of at least 3 months.
• Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to the first dose of study drug and agree to practice contraception from 30 days prior to the first dose of study drug through 30 days after the last dose of study drug; male subjects must undergo ligation surgery or agree to practice contraception from 7 days prior to the first dose through 30 days after the last dose of study drug and refuse to donate sperm; failure rate of contraception is \< 1% per year, and the typical birth control measures include double-barrier contraception, condom, oral or injectable contraceptives, intrauterine device, etc.
• Non-hematologic toxicities of prior therapy return to ≤ Grade 1 (NCI-CTCAE version 5.0), except alopecia.
• Male or female patients with relapsed or refractory triple-negative breast cancer who have received at least 2 prior lines of therapy or who have no standard treatment or who are unable to benefit from current therapy.
• ER-, PR-, HER2-.
• Patients diagnosed with ER+, HER2-, postmenopausal (≥ 18 years old) advanced breast cancer who have received one line of treatment, with evidence of local recurrence or metastasis, not suitable for surgical resection or radiotherapy with the purpose of cure, without clinical indication for chemotherapy, postmenopausal women who have not received systemic treatment;
• Menopause definition:

You may not qualify if:

• Patients who meet any of the following criteria should not be enrolled in this clinical study:
• Having received monoclonal antibody, chemotherapy, radiotherapy, or other investigational therapy within 4 weeks or 5 half-lives (whichever is shorter) before the start of dosing. Having received surgery or not recovered from surgery within 2 weeks before starting dose.
• Central nervous system metastasis or injury without a stable control (patients with stable disease for more than 3 months who have received intracranial radiotherapy，there is no need hormone therapy are allowed).
• Spinal cord compression was not treated with surgery and/or radical radiotherapy (previously diagnosed spinal cord compression clinically symptom or stable for ≥ 3 months after treatment is allowed.
• Leptomeningeal disease; uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage; uncontrolled tumor-related pain.
• Patients who have not recovered from toxic reactions caused by previous anti-tumor treatment (≥ NCI-CITCAE 5.0 grade 2, except alopecia); patients with uncontrolled diabetes (patients who are receiving stable insulin regimen or hypoglycemic agent regimen and are evaluated by specialists to have a stable blood glucose control are allowed).
• Patients with a history of coagulation disorders; patients requiring anticoagulant or antiplatelet therapy (aspirin dose ≤ 81 mg/d, orally and subcutaneous injection of low-molecular-weight heparin preventing of deep venous thrombosis is allowed).
• Patients with active infection of hepatitis B or C (except patients with liver cancer) or human immunodeficiency virus (HIV) infection or active pulmonary tuberculosis or other known active and/or uncontrolled infection.
• Patients with serious infections, including but not limited to infectious complications, bacteremia, and severe pneumonia requiring hospitalization; patients who received intravenous antibiotics within 2 weeks before enrollment (prophylactic antibiotics e.g., antibiotics for the prevention of urinary tract infection or chronic obstructive pulmonary disease are allowed).
• Any serious uncontrollable psychological or physical illness that would impair the patient's ability to follow protocol treatment, including but not limited to:Symptomatic congestive heart failure (congestive heart failure with New York Heart Association (NYHA) class ≥ III), unstable angina pectoris, arrhythmia, autoimmune diseases, infections and mental illness.
• Pregnant or lactating women. Any patient who gets pregnant during the trial is to be withdrawn from the study.
• Patients who have received prior IRE1 inhibitors.
• \. The investigator does not recommend re-treatment with paclitaxel because of toxicity.
• Patients have risk of life-threatening complications or organ spread in a short term.
• Known central nervous system uncontrolled or symptomatic metastases, the leptomeningeal metastasis.

Sponsors & Collaborators

• Orinove, Inc.: lead
• Fosun Pharma: collaborator

Study Sites (13)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Jilin Cancer Hospital

Changchun, 130000, China

Location

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, 310003, China

Location

Harbin medical University Cancer Hospital

Harbin, 150000, China

Location

Harbin Medical University Cancer Hospital

Heilongjiang, 150000, China

Location

The First Affiliated Hospital of Soochow University

Jiangse, 215006, China

Location

Harbin Medical University Cancer Hospital

Jilin, 130000, China

Location

Shandong Provincial Cancer Hospital

Jinan, 250000, China

Location

Shandong Provincial Cancer Hospital

Shandong, 250000, China

Location

Shanghai Pulmonary Hospital

Shanghai, 200433, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, 215006, China

Location

Tianjin Medical University Cancer Institute and Hospital

Tianjin, 300060, China

Location

The First Affiliated Hospital, Zhejiang University School of Medicine

Zhejiang, 310003, China

Location

Study Officials

• Lin Shen, MD

  Beijing Cancer Hospital and Peking University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 4, 2021
• First Posted: December 13, 2021
• Study Start: July 1, 2020
• Primary Completion: January 30, 2023
• Study Completion: January 30, 2025
• Last Updated: May 30, 2025

Record last verified: 2024-12

Locations

CN (13)