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

NCT06457919 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 24-103
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 12

Brief Summary

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).

Conditions

Prostate Cancer

Keywords

Tinengotinib (TT-00420); Androgen Receptor Signaling Inhibitors (ARSIs); TIP Study: Tinengotinib In Prostate Cancer; Prostate Cancer Clinical Trials Consortium, LLC (PCCTC); 24-103

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Rate of Radiographic Response (phase II)

  From start of study treatment until 6 months post study treatment start

Study Arms (2)

Tinengotinib with abiraterone acetate/prednisone

EXPERIMENTAL

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; Drug: abiraterone acetate with prednisone

Tinengotinib with enzalutamide

EXPERIMENTAL

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; Drug: Enzalutamide

Interventions

Tinengotinib DRUG

Tinengotinib will be administered daily for 28-day cycles. A flat dose of 10 mg PO once daily.

Also known as: TT-00420

Tinengotinib with abiraterone acetate/prednisone; Tinengotinib with enzalutamide

Enzalutamide DRUG

Enzalutamide 160 mg PO QD

Tinengotinib with enzalutamide

abiraterone acetate with prednisone DRUG

Abiraterone acetate 1000 mg PO QD in combination with prednisone 5 mg PO once or twice daily (QD or BID)

Tinengotinib with abiraterone acetate/prednisone

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Prostate cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• Nodal or visceral progression as defined by PCWG3-modified RECIST 1.1
• Appearance of 2 or more new lesions on a bone scan
• At least one of the following at study entry:
• 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
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• TransThera Sciences: collaborator

Study Sites (12)

Yale University (Data Collection Only)

New Haven, Connecticut, 06511, United States

RECRUITING

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Columbia University

New York, New York, 10032, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Duke University

Durham, North Carolina, 27710, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

NOT YET RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Abiraterone Acetate; Prednisone; enzalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols; Pregnadienes; Pregnanes

Study Officials

• Wassim Abida, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wassim Abida, MD, PhD

CONTACT

646-442-4633; abidam@mskcc.org

Michael Morris, MD

CONTACT

646-422-4469

Study Design

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

Model Details: In the Phase 1b portion of the study, participants will be enrolled sequentially in cohorts of 3 for each studied combination. The recommended Phase II dose (RP2D) of each combination will be estimated separately based on the de-escalation rules.

Study Record Dates

• First Submitted: June 5, 2024
• First Posted: June 13, 2024
• Study Start: June 4, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (12)