A Study of Tinengotinib (TT-00420) in Combination With Standard Treatments in People With Prostate Cancer

A Phase 1b/2 Study Evaluating the Activity of Tinengotinib (TT-00420) in Combination With Androgen Receptor Signaling Inhibitors (ARSIs) in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)

The purpose of this study is to find out whether tinengotinib in combination with abiraterone acetate and prednisone or enzalutamide is a safe treatment that causes few or mild side effects in people with metastatic castration-resistant prostate cancer (mCRPC).

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Tinengotinib; Drug: abiraterone acetate with prednisone; Drug: Enzalutamide

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Michael Morris, MD; Phone Number: 646-422-4469
• Study Contact Backup: Name: Wassim Abida, MD, PhD; Phone Number: 646-442-4633; Email: abidam@mskcc.org

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Recruiting
      • Yale University (Data Collection Only)
      • Contact: Samir Zaidi, MD, PhD; Email: samir.zaidi@yale.edu
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
      • Contact: Wassim Abida, MD, PhD; Phone Number: 646-442-4633
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
      • Contact: Wassim Abida, MD, PhD; Phone Number: 646-442-4633
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
      • Contact: Wassim Abida, MD, PhD; Phone Number: 646-442-4633
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk - Commack (Limited protocol activities)
      • Contact: Wassim Abida, MD, PhD; Phone Number: 646-442-4633
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (Limited protocol activities)
      • Contact: Wassim Abida, MD, PhD; Phone Number: 646-442-4633
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Michael Morris, MD; Phone Number: 646-422-4469
      • Contact: Wassim Abida, MD, PhD; Phone Number: 646-442-4633
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University
      • Contact: Mark Stein, MD; Phone Number: 212-305-5098
    • Uniondale, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (Limited Protocol Activities)
      • Contact: Wassim Abida, MD, PhD; Phone Number: 646-442-4633
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University
      • Contact: Hannah Dzimitrowicz McManus, MD; Phone Number: 919-668-6688
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Contact: Alexandra Sokolova, MD; Phone Number: 503-346-1500
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Not yet recruiting
      • Thomas Jefferson University Hospital
      • Contact: Raghava Levaka, MD; Phone Number: 215-890-3030

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants ≥ 18 years old, with signed informed consent
• Histologically confirmed carcinoma of the prostate (neuroendocrine differentiation is allowed, but pure small cell carcinoma is not permitted)
• Metastatic disease documented by at least 2 bone lesions on whole body radionuclide bone scan, or soft tissue disease documented by computed tomography (CT) scan/magnetic resonance imaging (MRI). Note: Metastatic disease seen only on PET imaging does not qualify.
• Current ongoing therapy and observed tolerance with full standard dose of abiraterone acetate (1000 mg QD) or enzalutamide (160 mg QD) at the time of study entry. Enzalutamide or abiraterone acetate must have been started at least 90 days before screening assessments. An interruption of dosing of a maximum of 30 days is permitted prior to resuming the agent. Please note: Patients who are on a reduced dose or are intolerant of abiraterone acetate or enzalutamide at screening will not be eligible for study participation.

• Progressive disease on enzalutamide or abiraterone acetate documented by PCWG3 criteria for study entry. Progressive disease is defined as at least one of the following:

  1. PSA progression defined as a minimum of 2 rising PSA levels with a minimum of a 1-week interval between each determination, reaching a minimum PSA value of 1.0 ng/mL.
  2. Nodal or visceral progression as defined by PCWG3-modified RECIST 1.1
  3. Appearance of 2 or more new lesions on a bone scan

• At least one of the following at study entry:

  1. RECIST 1.1 measurable disease at baseline; i.e., soft tissue tumor lesions or pathologically enlarged lymph nodes that can be accurately measured in at least one dimension OR
  2. a PSA of 2.0 ng/mL or above
• Participants must be medically or surgically castrated with ongoing androgen deprivation therapy (ADT) for ≥90 days or have documented history of bilateral orchiectomy.
• ECOG 0 - 2

• Adequate organ function confirmed at screening, as evidenced by:

  • Absolute neutrophil count ≥ 1.5 × 10^9 /L
  • Hemoglobin ≥ 9 g/dL
  • Platelets ≥ 75 × 10^9 /L
  • Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 2.5 × upper limit of normal (ULN) or ≤ 5.0 × ULN if liver metastases are present
  • Total bilirubin ≤ 1.5 × ULN; or < 2.5 × ULN if Gilbert syndrome or disease involving liver
  • Creatinine clearance >30 mL/min (Cockcroft-Gault formula)
  • Adequate blood coagulation function as evidence by an international normalized ratio (INR) ≤ 1.5 unless participant is on anticoagulants
• Tumor biopsy during screening is required if safe and feasible. If archival tissue is available from a previous biopsy performed within 90 days of screening assessments, a repeat screening biopsy is not required even if safe and feasible. If neither option is possible, archival tissue from any timepoint should be requested, if available.

Exclusion Criteria:

• The presence of any of the following criteria excludes a patient from participating in the study:
• Pure small cell carcinoma
• Previous exposure to multi-TKI therapies.
• Uncontrolled hypertension (persistent systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg) or known coronary artery disease with angina. Patients with known hypertension must be on antihypertensive medication with BPs generally <140/90 to be eligible.
• History of congestive heart failure of Class II-IV New York Heart Association criteria, or serious cardiac arrhythmia requiring treatment (except atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial infarction within 6 months of study entry, or prolongation of QTc interval to >480 msec using Fridericia formula (QTcF) at screening (except for participants with pacemakers, where there is no QTc cutoff).
• Any prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessments.
• Symptomatic and/or untreated CNS metastases.
• Pre-existing duodenal stent or any gastrointestinal disorder or defect which would interfere with absorption of study medication, as determined by the Investigator.
• Persistent requirement for corticosteroids at equivalent of >10 mg QD prednisone within 14 days before study treatment start.
• Other anticancer therapies within 3 weeks of study treatment start, or within 5 half-lives of study treatment start for non-cytotoxic oral agents, whichever is shorter; with the exception of androgen deprivation therapy, enzalutamide, or abiraterone acetate which should be continued through study treatment.
• Palliative radiation within 2 weeks of study treatment start.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tinengotinib with abiraterone acetate/prednisone; Tinengotinib will be administered daily for 28-day cycles. A flat dose of 10 mg PO once daily will be administered unless dose de-escalation is required in Phase 1b. Participants will receive tinengotinib with abiraterone acetate 1000 mg PO QD in combination with prednisone 5 mg PO once or twice daily (QD or BID)	Drug: Tinengotinib; Tinengotinib will be administered daily for 28-day cycles. A flat dose of 10 mg PO once daily.; Other Names: TT-00420; Drug: abiraterone acetate with prednisone; Abiraterone acetate 1000 mg PO QD in combination with prednisone 5 mg PO once or twice daily (QD or BID)
Experimental: Tinengotinib with enzalutamide; Tinengotinib will be administered daily for 28-day cycles. A flat dose of 10 mg PO once daily will be administered unless dose de-escalation is required in Phse 1b. Participants will receive Tinengotinib in combination with enzalutamide 160 mg PO QD.	Drug: Tinengotinib; Tinengotinib will be administered daily for 28-day cycles. A flat dose of 10 mg PO once daily.; Other Names: TT-00420; Drug: Enzalutamide; Enzalutamide 160 mg PO QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RP2D	Evaluate DLT occurrence to confirm safety and RP2D	From the start of study treatment through the DLT window (28 days)
Objective Response Rate (ORR)	by local investigator's assessment per PCWG3-modified RECIST v1.1 in participants with baseline measurable disease OR rate of PSA decline of ≥ 50% from baseline in patients with a baseline PSA of 2.0 ng/mL or above	up to 6months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Radiographic Response (phase II)	Rate of radiographic response by local investigator's assessment per PCWG3-modified RECIST v1.1 in participants with baseline measurable disease	From start of study treatment until 6 months post study treatment start

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: TransThera Sciences
• Investigators: Principal Investigator: Wassim Abida, MD, PhD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: June 5, 2024
• First Submitted That Met QC Criteria: June 5, 2024
• First Posted (Actual): June 13, 2024

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Tinengotinib (TT-00420); Androgen Receptor Signaling Inhibitors (ARSIs); TIP Study: Tinengotinib In Prostate Cancer; Prostate Cancer Clinical Trials Consortium, LLC (PCCTC); 24-103
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienediols; Androstenes; Androstanes; Abiraterone Acetate; Prednisone; enzalutamide
• Other Study ID Numbers: 24-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

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