ORIN1001 in Patients With Advanced Solid Tumors and Relapsed Refractory Metastatic Breast Cancer

A Phase 1/2, Open Label, Dose-Escalation and Expansion Study of Oral ORIN1001 With and Without Chemotherapy in the Treatment of Subjects With Solid Tumors

This study evaluates the anti-tumor effects of ORIN 1001 in patients with advanced solid tumors or relapsed refractory metastatic breast cancer (patients with progressive disease after receiving at least two lines of therapy in the advanced setting).

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Breast Cancer; Advanced Solid Tumor
• Intervention / Treatment: Drug: Abraxane

Detailed Description

This is a first in human, Phase 1/2, open label, dose escalation and dose expansion study that consists of two stages:

Phase 1: A dose escalation stage to determine the MTD/RP2D of ORIN1001 when given as a single agent in up to 30 subjects with advanced solid tumors. In addition, a dose escalation stage to determine the MTD/RP2D of daily ORIN1001 in combination with Abraxane given intravenously in up to 18 subjects with relapsed refractory metastatic breast cancer (TNBC or ER+ HER2-).

Phase 2: An expansion stage of ORIN1001 alone (Cohort A: TNBC) and in combination with Abraxane (Cohort B: Myc+; Cohort C: ER+ HER2-, and Cohort D: TNBC) to estimate efficacy in up to 120 subjects with relapsed refractory metastatic breast cancer.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Tucson, Arizona, United States, 85719
      • University of Arizona Cancer Center
  • California
    • Burbank, California, United States, 91505
      • UCLA Health Burbank Specialty Care
    • Laguna Hills, California, United States, 92653
      • UCLA Health Laguna Hills Cancer Care
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center (UCIMC) - Chao Family Comprehensive Cancer Center
    • Westwood, California, United States, 90024
      • University of California Los Angeles (UCLA) - Jonsson Comprehensive Cancer Center (JCCC) - Oncology Center - Westwood
  • Colorado
    • Denver, Colorado, United States, 80045
      • University of Colorado Anschutz Medical Campus
    • Highlands Ranch, Colorado, United States, 80129
      • Highlands Ranch Hospital
    • Lone Tree, Colorado, United States, 80124
      • University of Colorado Lone Tree Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital and Clinics - Sylvester Comprehensive Cancer Center
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St Lukes Cancer Institute
  • New York
    • Buffalo, New York, United States, 14203
      • Roswell Park Comprehensive Cancer Center (RPCCC) (Roswell Park Cancer Institute (RPCI))
    • New Hyde Park, New York, United States, 11042
      • Northwell Health
    • New Hyde Park, New York, United States, 11042
      • Northwell Heath Cancer Institute
    • New York, New York, United States, 10016
      • NYU Langone Health
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

For dose escalation with ORIN1001 alone:

-Male or female with advanced solid tumors for which no effective standard of care treatments are available

For dose escalation with ORIN1001 in combination with Abraxane:

-Males or females with relapsed refractory metastatic breast cancer (TNBC or ER+, HER2-) must have progressed through at least 2 lines of therapy and for whom there are no available therapies that confer a clinical benefit

For dose expansion:

a. Males or females with relapsed refractory metastatic breast cancer including:

1. TNBC (i.e. estrogen receptor (ER)-, progesterone receptor-, and human epidermal growth factor receptor 2 [HER2]-)
2. ER+ HER2- breast cancer

Inclusion Criteria for Dose Escalation and Dose Expansion

1. Adults aged ≥ 18 years
2. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
3. Life expectancy of 3-4 months
4. Have at least one measurable lesion per RECIST 1.1

5. Have adequate organ function, including all of the following:

   1. Adequate bone marrow reserve as defined by: ANC≥1.0 x 10 9/L; platelet count ≥75 x 10 9/L; hemoglobin ≥9 g/dL
   2. Hepatic: total bilirubin ≤2 x ULN, transaminases (AST/SGOT and/or ALT/SGPT) ≤ 3X ULN;alkaline phosphatase ≤ 5 x ULN
   3. Renal: 24-hour creatinine clearance ≥ 30 mL/min calculated
6. Adequate tissue sample from either archival tumor tissue or fresh biopsy of tumor at the screening for tumor genotyping.
7. Male subjects must be surgically sterile or must agree to use physician approved contraception for 7 days prior to the first study drug administration to 30 days after the last dose of study treatment.
8. Women of childbearing potential must have negative serum pregnancy test within 14 days prior the first administration of study drug and agree to use physician-approved contraception from 30 days prior to the first study drug administration to 30 days following the last study drug administration.
9. Ability to understand and willingness to sign an informed consent prior to any study specific procedures.
10. Resolution of all toxicities (except alopecia) from prior therapy to ≤ Grade 1 (CTCAE v5)

Exclusion Criteria:

1. Does not meet inclusion criteria

2. Received any of the following within the specified time frame prior to the first administration of study drug:

   i. Excluding those with a history of coagulopathy ii. Excluding those who require concurrent use of anti-coagulants or anti-platelet medication, with exception of aspirin doses ≤ 81 mg/day, prophylaxis subcutaneous (SC) heparin or SC low-molecular weight heparin for deep vein thrombosis (DVT) prophylaxis or heparin flushes to maintain IV catherer patency iii. Excluding subjects that have Prothrombin time (PT)/international normalized ratio (INR) or activated partial thromboplastin time (aPTT) >1.5 x ULN b.Prior chemotherapy or other systemic anticancer therapy within 3 weeks or 5 times the plasma half-life of the drug, whichever is shorter; c.Prior radiotherapy within 2 weeks; d.Major surgery within 2 weeks; e.Prior treatment with investigational drugs within 4 weeks; f. Myocardial infarction, uncontrolled angina,severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, within 6 months prior to the fist dose of study drug

3. Greater than Class II heart failure using New York Heart Association (NYHA) criteria
4. The subject has uncontrolled human immunodeficiency virus (HIV) infection or active hepatitis B or C infection or other known active and/or uncontrolled infection
5. Active autoimmune disease that is not appropriately controlled with treatment

6. Active malignancy with the exception of:

   1. adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer
   2. adequately treated stage I cancer from which the subject is currently in remission, or
   3. any other cancer from which the subject has been disease-free for ≥3 years;
7. Any serious uncontrolled medical or psychological disorder that would impair the ability to receive protocol therapy
8. Any condition which places the subject at unacceptable risk or confounds the ability of the investigator to interpret study data
9. The subject is pregnant or lactating woman. Any woman who becomes pregnant during the study will be withdrawn from the study.
10. Known active uncontrolled or symptomatic brain metastases. Patients with a history of such metastases that have been treated and are stable ≥28 days may be enrolled. Patients with no steroid use for at least 2 weeks prior to the time of enrollment are permitted.
11. Failed to respond to the most recent dose of Abraxane and must have been received at least 12 months prior to starting treatment.(combination arm only)
12. Greater than Grade 1 neuropathy (combination arm only)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Dose Escalation; Advanced solid tumors or metastatic breast cancer: Treatment with a single oral agent, ORIN1001. Relapsed, refractory metastatic breast cancer: Treatment with a combination of ORIN1001 and Abraxane.	Drug: Abraxane; The doses of ORIN1001 in both dose escalation and dose expansion will be 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600mg, 800 mg, 1,000 mg, 1,200 mg Weekly paclitaxel will be 80 mg/m2 given intravenously for the dose escalation and dose expansion phases. cohorts as follows: 100 mg, 200 mg, 400 mg, 600 mg, 800 mg, 1,000 mg, 1,300 mg and 1,500 mg administered for 21 days (one cycle).; Other Names: ORIN1001
Experimental: Phase 2: Dose Expansion; Relapsed refractory metastatic breast cancer that are Triple negative, ER+ or HER2- and treated with a single agent (ORIN1001) or in combination with ORIN1001 and Abraxane.	Drug: Abraxane; The doses of ORIN1001 in both dose escalation and dose expansion will be 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600mg, 800 mg, 1,000 mg, 1,200 mg Weekly paclitaxel will be 80 mg/m2 given intravenously for the dose escalation and dose expansion phases. cohorts as follows: 100 mg, 200 mg, 400 mg, 600 mg, 800 mg, 1,000 mg, 1,300 mg and 1,500 mg administered for 21 days (one cycle).; Other Names: ORIN1001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the safety of MTD/RP2D of single-agent daily ORIN1001 when administered orally in subjects with advanced solid tumors: NCI CTCAEv5 Common Toxicity Criteria	To determine the safety of the maximal tolerated dose/ recommended Phase 2 dose (MTD/RP2D). Incidence of the safety population will consist of all subjects who received a dose of study drug. Treatment-related AE is any untoward medical occurrence attributed to study drug in a participant who received study drug. Adverse events will be evaluated and recorded according to NCI CTCAEv5 Common Toxicity Criteria and will use medical terminology based on the Medical Dictionary for Regulatory Activities Terminology (MedDRA).	From first dose up to 21 days after last dose
To determine the safety MTD/RP2D of daily ORIN1001 when administered orally in combination with paclitaxel given intravenously at 175 mg/m2 once every three weeks in subjects with relapsed refractory metastatic breast cancer	Incidence of the safety population will consist of all subjects who received a dose of study drug. Treatment-related AE is any untoward medical occurrence attributed to study drug in a participant who received study drug. Adverse events will be evaluated and recorded according to NCI CTCAEv5 Common Toxicity Criteria and will use medical terminology based on the Medical Dictionary for Regulatory Activities Terminology (MedDRA).	From first dose up to 21 days after last dose
To evaluate the safety and tolerability of single-agent daily ORIN1001 when administered orally in the dose escalation and expansion stages of the study: NCI CTCAEv5 Common Toxicity Criteria	Incidence of the safety population will consist of all subjects who received a dose of study drug. Treatment-related AE is any untoward medical occurrence attributed to study drug in a participant who received study drug. Adverse events will be evaluated and recorded according to NCI CTCAEv5 Common Toxicity Criteria and will use medical terminology based on the Medical Dictionary for Regulatory Activities Terminology (MedDRA).	From first dose up to 21 days after last dose
To evaluate the safety and tolerability of daily ORIN1001 when administered orally in combination with Abraxane given intravenously at 100 mg/m2 once weekly for 3 weeks in the dose escalation and expansion stages of the study	Incidence of number of participants with clinically significant change in vital signs. Vital signs include body weight, body temperature, resting blood pressure, pulse and respiratory rate.	From first dose up to 28 days after last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the peak concentrations (Cmax) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.	Determine the dose-dependent peak concentrations (Cmax) of ORIN1001 by direct inspection of the plasma concentration-time curves of ORIN1001 following single and repeat oral doses of ORIN 1001 as a single agent and in combination with Abraxane.	2 months
To evaluate the time to peak concentrations (Tmax) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.	Determine the dose-dependent time to peak concentrations (Tmax) of ORIN1001 by direct inspection of the plasma concentration-time curves of ORIN1001 following single and repeat oral doses of ORIN 1001 as a single agent and in combination with Abraxane.	2 months
To evaluate the area under the plasma concentration versus time curve (AUC) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.	Determine the dose-dependent area under the plasma concentration versus time curve (AUC) for ORIN1001 following single doses of ORIN 1001 as a single agent and in combination with Abraxane.	2 months
To evaluate the last time point with a quantifiable concentration (AUClast) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.	Determine the dose-dependent plasma levels of ORIN1001 from the time of dosing to the last time point with a quantifiable concentration (AUClast) of ORIN1001 following single doses of ORIN 1001 as a single agent and in combination with Abraxane.	2 months
To evaluate the plasma concentration end of a dosing interval (Ctau) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.	Determine the dose-dependent plasma concentrations (Cmax) of ORIN1001 as single agent or in combination with Abraxane at the end of a dosing interval (Ctau), where tau is 24 hours for once daily dosing.	2 months
To evaluate the average plasma concentration (Cav) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.	Determine the average plasma concentration (Cav) of ORIN1001 as single agent or in combination with Abraxane during the dosing interval.	2 months
To evaluate the minimum plasma concentrations (Cmin) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.	Determine the the minimum plasma concentrations (Cmin) reached by ORIN1001 as single agent or in combination with Abraxane prior to administration of a second dose.	2 months
To evaluate the elimination constant (λz) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.	Determine the dose-dependent plasma elimination constant (λz) for ORIN1001 as a single agent or in combination with Abraxane.	2 months
To evaluate the terminal half-life (T1/2) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.	Determine the dose-dependent terminal plasma half-life of ORIN1001 (T1/2) as a single agent or in combination with Abraxane.	2 months
To evaluate the plasma clearance (CL/f) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.	Determine the dose-dependent apparent total plasma clearance (CL/f) of ORIN1001 after oral administration as a single agent or in combination with Abraxane.	2 months
To evaluate the volume of distribution (Vz/f) of ORIN1001 after oral administration as a single agent and in combination with Abraxane.	Determine the apparent volume of distribution (Vz/f) during terminal phase after oral administration of ORIN1001 as a single agent or in combination with Abraxane.	2 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To quantify the objective response rate (ORR) of ORIN1001 alone and in combination with Abraxane	To quantify the proportion of patients with an objective tumor response as defined by RECIST 1.1 response criteria (SD, PR, CR).	Baseline up to approximately 2 years
To quantify the difference in the objective response rate (ORR) in relapsed refractory metastatic breast cancer showing potentially response-predictive aberrations of MYC and other genes under ORIN1001 alone or in combination with Abraxane	To quantify the proportion of patients with an objective tumor response as defined by RECIST 1.1 response criteria (SD, PR, CR).	Baseline up to approximately 2 years
To measure the response duration in patients receiving ORIN1001 alone and in combination with Abraxane.	To measure the duration of response from the time point of first established response (SD, PR, CR) until the time of documented tumor progression.	Baseline up to approximately 2 years
To quantify the difference in the duration of response in relapsed refractory metastatic breast cancer showing potentially response-predictive aberrations of MYC and other genes under ORIN1001 alone or in combination with Abraxane	To measure the duration of response from the time point of first established response (SD, PR, CR) until the time of documented tumor progression.	Baseline up to approximately 2 years
To measure the time to response in patients receiving ORIN1001 alone and in combination with Abraxane.	To measure the time from cycle 1 day 1 dose to the time of first documentation of tumor response (SD, PR, CR).	Baseline up to approximately 2 years
To quantify the difference in the time to response in relapsed refractory metastatic breast cancer showing potentially response-predictive aberrations of MYC and other genes under ORIN1001 alone or in combination with Abraxane.	To measure the time from cycle 1 day 1 dose to the time of first documentation of tumor response (SD, PR, CR).	Baseline up to approximately 2 years
To measure the duration of progression free survival (PFS) in patients receiving ORIN1001 alone and in combination with Abraxane	To measure the time from cycle 1 day 1 dose administration to the time of documented disease progression or death from any cause.	Baseline up to approximately 2 years
To quantify the difference in the progression free survival (PFS) in relapsed refractory metastatic breast cancer showing potentially response-predictive aberrations of MYC and other genes under ORIN1001 alone or in combination with Abraxane.	To measure the time from cycle 1 day 1 dose administration to the time of documented disease progression or death from any cause.	Baseline up to approximately 2 years
To measure the duration of overall survival (OS) under treatment with ORIN1001 alone and in combination with Abraxane.	To measure the duration of overall survival (OS) which is the time from Cycle 1 day 1 until death from any cause.	Baseline up to approximately 2 years
To quantify the difference in overall survival (OS) in relapsed refractory metastatic breast cancer showing potentially response-predictive aberrations of MYC and other genes under ORIN1001 alone or in combination with Abraxane	To measure the duration of Overall Survival (OS) which is the time from Cycle 1 day 1 until death from any cause.	Baseline up to approximately 2 years

Collaborators and Investigators

• Sponsor: Orinove, Inc.
• Investigators: Principal Investigator: Mothaffar F Rimawi, MD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2019
• Primary Completion (Actual): January 11, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: April 23, 2019
• First Submitted That Met QC Criteria: May 14, 2019
• First Posted (Actual): May 15, 2019

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Solid tumors, Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Albumin-Bound Paclitaxel
• Other Study ID Numbers: ORIN1001-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No