Study of ON 123300 in Patients With Advanced Cancer

Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetics of ON 123300 Capsules Administered Orally as Escalating Daily Doses in Patients With Advanced Cancer Relapsed or Refractory to at Least One (1) Prior Line of Therapy

This study will investigate the safety of the drug ON 123300 at increasing doses to determine the best dose to use in future clinical trials.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumors, Adult
• Intervention / Treatment: Drug: ON123300

Detailed Description

After being informed about the study including potential risks, patients giving written informed consent will proceed to a screening period when assessments will be performed to determine whether the patient is eligible to participate in the study. If the patient is eligible, they will start to receive ON 123300 as capsules every day. On day 1 and Day 8 of the study, patients will be required to provide eight blood samples to allow measurement of the amount of drug in their blood. Three ECGs will also be performed during this time. Patients will continue to receive ON 123300 until disease progression, unacceptable toxicity, or patient or physician decision to stop.

The first group of patients will receive 40mg of ON 123300 daily, the next group 80mg of ON 123300, the 120mg, etc. until the correct dose has been determined for future studies.

Patients will visit the clinic on Days 1, 2, 8, and 9, then weekly for the first month, then every two weeks for two more months, then every month.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • START Midwest
      • Contact: Julie Burns, BS; Phone Number: 616-954-5559; Email: Julie.burns@startmidwest.com
      • Principal Investigator: Manish Sharma, MD
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Recruiting
      • Greenville Health System, Institute for Oncology Clinical Research
      • Contact: Fiona Davidson; Phone Number: 864-455-3600; Email: Fiona.Davidson@prismahealth.org
      • Contact: Lisa Johnson; Phone Number: 864-455-3600; Email: lisa.johnson@prismahealth.org
      • Principal Investigator: Ki Chung, MD
  • Texas
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Mary Crowley Cancer Research
      • Principal Investigator: Douglas Orr, MD
      • Contact: Douglas Orr, MD; Phone Number: 972-566-3000; Email: referral@marycrowley.org

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. ≥ 18 years of age the time of signing the informed consent form (ICF);

2. Histological or cytological evidence of advanced and/or metastatic cancer,

   1. For Dose Escalation Cohorts, patients with measurable or non-measurable disease;
   2. For RP2D Expansion Cohort, patients with measurable disease;
3. Patients must have received and failed at least one prior approved treatment, or have no therapeutic options available as deemed appropriate by their treating physician;
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of < 2;
5. Life expectancy of > 3 months;
6. Patients must be able to swallow oral capsules;
7. Women of child-bearing potential must have a negative serum screening for pregnancy within 14 days prior to screening. Women and men of child-bearing potential must agree to use highly effective methods of birth control before entry and throughout the study, for up to 12 weeks following the last dose of ON 123300.
8. Patients must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted;
9. Patients must have the ability to understand the nature of the study and any hazards of participating in the study and communicate satisfactorily with the investigator to participate in the study.
10. Patients must be willing and able to adhere and comply to the requirements of the entire study including study visit schedule and other protocol requirements;

11. Have adequate organ function, including:

    a. Hematologic: i. absolute neutrophil count (ANC) ≥1.0 × 109/Liter (L) ii. platelets ≥100 × 109/L, and iii. hemoglobin ≥8 g/deciliter (dL). b. Hepatic: i. Total bilirubin ≤1.5 times the upper limit of normal (ULN) and ii. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 times ULN (or ALT and AST ≤5 times ULN if liver metastases are present).

    c. Renal: i. Serum creatinine ≤1.5 times ULN. or estimated creatinine clearance (calculated according to normal institutional practice) greater than 50 ml/min.

Exclusion Criteria:

1. Patients that have any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in the study or present an unacceptable risk to the patient;

2. Patients at risk for Torsades de pointes (TdP):

   1. Who have a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >480 milliseconds (ms) (CTCAE grade 1) using Fredericia's QT correction formula, or
   2. who have a history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome), or
   3. who are currently taking medications that prolong the QT/QTc interval;
3. Patients with a diagnosis of hematological malignancies except for non-Hodgkin's lymphoma;
4. Have received recent chemotherapy, hormonal therapy, other targeted cancer treatment, or investigational therapy within 14 days of planned first dose;
5. Patients currently taking or within 5 half-lives of taking strong inducers and inhibitors of CYP2C8 and CYP3A4;
6. History of allergic reaction attributed to compounds of similar chemical or biologic composition/structure to ON 123300 (e.g. prior CDK4/6 inhibitors);
7. Uncontrolled intercurrent illness including but not limited to ongoing or active infection, bleeding, congestive heart failure, unstable angina, cardiac arrhythmia, oxygen-dependent lung disease, psychiatric illness/social situations that limit participation compliance with study procedures and requirements;
8. Patients with a recent history of venous thromboembolic events, defined as event occurring ≤ 6 months prior to screening and also currently on therapy;
9. Patients with baseline Grade ≥ 2 diarrhea;
10. Patients with Grade ≥ 3 hypercalcemia (Corrected serum calcium > 12.5 mg/dL);
11. Pregnant or nursing mothers;
12. Have had major surgery within 14 days prior to screening to allow for post-operative healing of the surgical wound and site(s).
13. Have received recent (within 28 days prior to screening) live attenuated vaccines.
14. Have active bacterial, fungal or detectable viral infection (e.g. Human Immunodeficiency Virus or Hepatitis B or Hepatitis C).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ON 123300; ON 123300 capsules at increasing doses per cohort, starting at 40 mg	Drug: ON123300; ON 123300 hard gelatin capsules; Other Names: HX 301

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose Limiting Toxicities (DLT)	Incidence of protocol defined toxicities that would result in stopping dosing	First 28 days of dosing
Incidence of adverse events (AE)	Adverse events as measured by CTCAE version 5.0	Consent to 30 days after last dose
Abnormal Laboratory Test results	Changes and trends in standard hematology and chemistry blood tests	Consent to 30 days after last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establish the recommended phase 2 dose (RP2D)	Incidence of DLTs	First 28 day cycle
Pharmacokinetics of ON 123300 and 2 metabolites - Cmax	Maximum plasma concentration	Intense PK on Cycle1 Day1 and Day 8; Single samples pre-dose on Cycle 2 Day 1 and Cycle 3 Day 1 (each cycle is 28 days)
Pharmacokinetics of ON 123300 and 2 metabolites - Tmax	Time to reach Cmax	Intense PK on Cycle1 Day1 and Day 8; Single samples pre-dose on Cycle 2 Day 1 and Cycle 3 Day 1 (each cycle is 28 days)
Pharmacokinetics of ON 123300 and 2 metabolites - AUClast	The area under the plasma concentration-time curve (AUC) calculated to the last quantifiable sample	Intense PK on Cycle1 Day1 and Day 8; Single samples pre-dose on Cycle 2 Day 1 and Cycle 3 Day 1 (each cycle is 28 days)
Pharmacokinetics of ON 123300 and 2 metabolites - T1/2	Terminal phase elimination half-life	Intense PK on Cycle1 Day1 and Day 8; Single samples pre-dose on Cycle 2 Day 1 and Cycle 3 Day 1 (each cycle is 28 days)
Pharmacokinetics of ON 123300 and 2 metabolites - CL/F	The apparent oral clearance	Intense PK on Cycle1 Day1 and Day 8; Single samples pre-dose on Cycle 2 Day 1 and Cycle 3 Day 1 (each cycle is 28 days)
Pharmacokinetics of ON 123300 and 2 metabolites - Vss	Steady state volume of distribution	Intense PK on Cycle1 Day1 and Day 8; Single samples pre-dose on Cycle 2 Day 1 and Cycle 3 Day 1 (each cycle is 28 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preliminary efficacy of ON 123300	Objective responses by RECIST	Through study completion, an average of 6 months

Collaborators and Investigators

• Sponsor: Onconova Therapeutics, Inc.
• Investigators: Study Director: Michael E Saunders, MD, Onconova Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2021
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: January 29, 2021
• First Submitted That Met QC Criteria: February 2, 2021
• First Posted (Actual): February 4, 2021

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 19-01

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