Phase 1 Study of Oral TP-1454

NCT04328740 | Completed Phase 1 FDA Drug

• 1 other identifier: TP-1454-101
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 11

Brief Summary

This study will evaluate the safety and tolerability of oral TP-1454 in patients with advanced metastatic or progressive solid tumors and anal cancer.

Conditions

Advanced Solid Tumor; Anal Cancer

Keywords

Sumitomo Pharma Oncology; Phase 1; Advanced Solid Tumors; Refractory; Anal cancer

Outcome Measures

Primary Outcomes (3)

• Determine maximum tolerated dose (MTD)

  MTD will be determined based upon toxicity grades which are defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 5.0.

  50 months

• Determine recommended Ph2 dose (RP2D) of TP-1454

  To establish the RP2D for future studies with TP-1454. MTD, PK and PD data to be reviewed.

  50 months

• Incidence of SAEs and AEs resulting in study discontinuation, as assessed by NCI NTCAE v5.0

  With approval of protocol amendment 7, the primary objective of this study is to continue to monitor the safety and tolerability of TP-1454 in ongoing patients.

  From date of treatment through 30 days after End of Treatment, an average of 6 months

Secondary Outcomes (2)

• Determine incidence of dose-limiting toxicities (DLTs)

  28 days

• Determine antitumor activity of TP-1454.

  50 months

Study Arms (1)

TP-1454

EXPERIMENTAL

Flat dose once or twice daily

Drug: TP-1454 monotherapy

Interventions

TP-1454 monotherapy DRUG

Flat dose once or twice daily, alone

TP-1454

Eligibility Criteria

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

You may qualify if:

• Patients to be enrolled during Dose Escalation with capsules must have a histologically confirmed diagnosis of advanced metastatic or progressive solid tumor who are refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition (enrollment complete).
• Following approval of Amendment 5.0, patients to be enrolled during Dose Escalation with Tablets must have a histologically confirmed diagnosis of anal cancer and:
• have received at least one line of systemic platinum-based therapy in the advanced setting; (Note: Systemic platinum therapy given in the adjuvant setting will meet this criterion if there is recurrence or metastasis within 6 months of completing adjuvant therapy.); and
• have received no more than 3 total lines of systemic therapy in the advanced setting.
• Have measurable disease as outlined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
• Be ≥18 years of age
• Have a negative pregnancy test (if female of childbearing potential)
• Have acceptable liver function:
• Bilirubin ≤1.5x upper limit of normal (ULN) (unless associated with Gilbert syndrome)
• Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) and alkaline phosphatase ≤2.5x ULN\* \*If liver metastases are present, then ≤ 3x ULN is allowed.
• Have acceptable renal function: calculated creatinine clearance ≥60 mL/min (using Cockcroft Gault formula)
• Have acceptable hematologic status:
• Granulocyte ≥1500 cells/mm3
• Platelet count ≥100,000 (plt/mm3)

You may not qualify if:

• New York Heart Association Class III or IV cardiac disease, or myocardial infarction, severe unstable angina, coronary/peripheral artery bypass graft, congestive heart failure within the past 6 months or evidence of ischemia on electrocardiogram (ECG) within 14 days prior to Cycle 1/Day 1
• Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of \>450 msec in men and \>470 msec in women
• Have a seizure disorder requiring anticonvulsant therapy
• Have untreated central nervous system (CNS) metastases including carcinomatous meningitis. Patients with definitively treated (radiotherapy or surgery) CNS metastases may be eligible if asymptomatic and not receiving corticosteroids in excess of prednisone 10 mg (or equivalent) per day for ≥2 weeks before first dose of TP-1454
• Have hypoxemia (defined as resting O2 saturation of ≤90% breathing room air)
• Have symptomatic interstitial lung disease
• Have undergone major surgery within 2 weeks prior to Cycle 1/Day 1
• Have active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
• Are pregnant or nursing
• Received treatment with radiation therapy to a target lesion, surgery, chemotherapy, or investigational therapy within 28 days or 5 half-lives, whichever occurs first, prior to study entry (6 weeks for nitrosoureas or mitomycin C)
• Are unwilling or unable to comply with procedures required in this protocol
• Dose escalation in solid tumors with capsules only: Have known infection with hepatitis B, or hepatitis C. Patients with history of chronic hepatitis that is currently not active are eligible
• Have a serious nonmalignant disease (eg, hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor
• Are currently receiving any other investigational agent
• Have exhibited allergic reactions to a similar structural compound, biological agent, or formulation(s)

Sponsors & Collaborators

• Sumitomo Pharma America, Inc.: lead

Study Sites (11)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

University of Southern California - Norris Cancer Center and Hoag Memorial Hospital

Los Angeles, California, 90033 and 92663, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Comprehensive Cancer Center of Nevada

Las Vegas, Nevada, 89169, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Texas Oncology Baylor Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Anus Neoplasms

Condition Hierarchy (Ancestors)

Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases

Study Officials

• Jian Li, MD

  Sumitomo Pharma America, Inc.

  STUDY DIRECTOR

Study Design

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

Model Details: Open label

Study Record Dates

• First Submitted: March 20, 2020
• First Posted: March 31, 2020
• Study Start: July 8, 2020
• Primary Completion: April 25, 2025
• Study Completion: April 25, 2025
• Last Updated: May 1, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)