Phase 1 Clinical Study of GT-220F in Subjects With Metastatic Castration Resistant Prostate Cancer (mCRPC)

NCT06866795 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: GT-220F-101
• Study Type: interventional
• Target: 42
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to test GT-220F in patients with metastatic castration resistant prostate cancer and learn about the best dose required for further study. Participants will be adults with metastatic castration resistant prostate cancer. The main questions the study aims to answer are: 1) What medical problems do participants have when taking GT-220F? 2) What dose strength is best to use in further clinical trials? Participants will be asked to

• take GT-220F every day
• take medical tests every week

Conditions

Metastatic Castration Resistant Prostate Cancer

Keywords

prostate cancer; metastatic prostate cancer; castration resistant prostate cancer; PTEN-loss; mCRPC; PTEN-deficient; PI3K; PI3Kbeta

Outcome Measures

Primary Outcomes (4)

• Dose Limiting Toxicity (DLT)

  Number and severity of dose limiting toxicity during Cycle 1 of GT-220F administration during dose escalation

  at the end of Cycle 1 (each cycle is 28 days)

• Maximum Tolerated Dose (MTD)

  Maximum tolerated dose, determined by the occurrence of dose limiting toxicities during Cycle 1 of GT-220F administration

  at the end of Cycle 1 (each cycle is 28 days)

• Recommended Phase 2 Dose

  Recommended Phase 2 dose, determined by evaluation of maximum tolerated dose, dose limiting toxicities, and pharmacokinetics during Cycle 1 of GT-220F administration

  at the end of Cycle 1 (each cycle is 28 days)

• Adverse Events

  Adverse events, characterized by type, frequency and relationship to the intervention (GT-220F) during administration of GT-220F and for 30 days after stopping administration of GT-220F

  from date of randomization to date of progression, assessed up to 50 weeks

Secondary Outcomes (12)

• Objective tumor response rate (ORR)

  from date of randomization to date of progression, assessed up to 50 weeks

• Duration of objective tumor response (DOR)

  from date of randomization to date of progression, assessed up to 50 weeks

• Disease control rate (DCR)

  from date of randomization to date of progression, assessed up to 50 weeks

• Radiographic progression-free survival (PFS)

  from date of randomization to date of progression, assessed up to 50 weeks

• Prostate specific antigen measurements - change from baseline

  from date of randomization to date of progression, assessed up to 50 weeks

Study Arms (6)

GT-220F Dose Level 1

EXPERIMENTAL

GT-220F 50mg, oral capsule, once a day

Drug: GT-220F capsule

GT-220F Dose Level 2

EXPERIMENTAL

GT-220F increased dose level to be determined, oral capsule, once or twice a day

Drug: GT-220F capsule

GT-220F Dose Level 3

EXPERIMENTAL

GT-220F increased dose level to be determined (if needed), oral capsule, once or twice a day

Drug: GT-220F capsule

GT-220F Dose Level 4

EXPERIMENTAL

GT-220F increased dose level to be determined (if needed), oral capsule, once or twice a day

Drug: GT-220F capsule

GT-220F Dose Level 5

EXPERIMENTAL

GT-220F increased dose level to be determined (if needed), oral capsule, once or twice a day

Drug: GT-220F capsule

GT-220F Dose Expansion

EXPERIMENTAL

GT-220F recommended phase 2 dose, oral capsule, once or twice a day

Drug: GT-220F capsule

Interventions

GT-220F capsule DRUG

GT-220F capsule for oral administration

Also known as: 9-((R)-1-((3,5-difluorophenyl)amino)ethyl)-7-((R)-3-(dimethylamino)pyrrolidine-1-carbonyl)-2-morpholino-4H-pyrido[1,2-a]pyrimidin-4-one fumarate

GT-220F Dose Expansion; GT-220F Dose Level 1; GT-220F Dose Level 2; GT-220F Dose Level 3; GT-220F Dose Level 4; GT-220F Dose Level 5

Eligibility Criteria

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

You may qualify if:

• Males ≥ 18 years of age. Because no dosing or adverse event data are currently available on the use of GT-220F in subjects \<18 years of age, children are excluded from this study.
• In Dose Escalation (Part 1) Only - subjects must have histologically confirmed recurrent or progressive metastatic castration resistant prostate cancer (mCRPC). In Dose Expansion (Part 2) Only - subjects must have histologicaly confirmed recurrent or progressive mCRPC with alterations in the PTEN gene (mutations or deletions) or PIK3CB gene (activating mutations or amplifications) as determined by Next-Generation Sequencing.
• Subjects must have received at least one previous AR pathway inhibitor (enzalutamide, apalutamide, darolutamide, abiraterone acetate) for biochemically recurrent or metastatic prostate cancer.
• Ongoing ADT with a lutenizing hormone releasing hormone agonist/antagonist or bilateral orchiectomy that results in serum testosterone \< 50 ng/dL.
• Subjects must have shown evidence of radiological and/or prostate specific antigen (PSA) progression. For PSA progression, there must be at least 2 sequential rises at a minimum of 1-week intervals. The first PSA value must be ≥ 2 ng/mL. Progression of measurable disease (RECIST 1.1 criteria) or presence of at least two new bone lesions (Prostate Cancer Working Group 3 criteria).
• Subjects must have recovered to grade ≥ 2 or pre-treatment baseline from clinically significant toxic effects of prior therapy.
• ECOG performance status \>2
• Subjects must have adequate organ and marrow function as defined below:
• absolute neutrophil count ≥ 1,500/mcL
• hemoglobin ≥ 9g/dL
• platelets ≥ 75,000/mcL
• total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (subjects with Gilbert syndrome are allowed if direct bilirubin within normal limits)
• AST(SGOT)/ALT(SGPT) ≤ 3 x institutional ULN
• creatinine ≤ 1.5 xULM mg/dL OR a calculated creatinine clearance ≥50mL/min.
• Left ventricular ejection fraction at least 50% by echocardiogram or multigated acquisition scan.

You may not qualify if:

• Evidence of oncogenic mutations in PIK3CA, RAS or receptor tyrosine kinase (RTK) genes (EGFR, ALK).
• Subjects who have had prior treatment with PI3K inhibitors with beta and/or delta isoform activity: GSK2636771, AZD 8186, idelalisib, copanlisib, duvelisib, umbralisib.
• Subjects who have had any cancer-directed immunomodulatory or molecularly-targeted agent or monoclonal antibody within 14 days prior to initiation of study drug.
• Subjects who have used any investigational agents within 28 days or 5 half-lives from study initiation, whichever is shorter.
• Subjects who have increasing corticosteroid requirement or a dose \>6 mg per day of dexamethasone or equivalent dose of other corticosteroids within 7 days prior to study initiation.
• Subjects who received radiation therapy within 4 weeks prior to enrollment, unless there is surgical confirmation of recurrent disease or evidence of new enhancing recurrent disease outside of the prior radiotherapy treatment field.
• Subjects who have had major surgery within 28 days prior to registration.
• Subjects with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to GT-220F.
• Subjects with known human immunodeficiency virus or acquired immunodeficiency syndrome-related illness.
• Subjects with any of the following within 6 months prior to initiation of study drug: uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack.
• Pulmonary embolism within 1 month prior to initiation of study drug.
• Unstable cardiac dysrhythmias or persistent prolongation of the QTc (Fridericia) interval to \>470msec.
• Evidence of Grade ≥ 2 intracranial hemorrhage.
• Subjects with any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with the interpretation of study results and, in the Investigator's opinion, would make the subject inappropriate for entry into this study.
• Subjects with uncontrolled intercurrent illness, including active or clinically unstable bacterial, viral or fungal infection requiring systemic therapy.

Sponsors & Collaborators

• Geode Therapeutics Inc.: lead

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Alok Tewari, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haiying Peng

CONTACT

6178233851; haiying.peng@geodetx.com

Jean J. Zhao, PhD

CONTACT

jean.zhao@geodetx.com

Study Design

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

Study Record Dates

• First Submitted: February 28, 2025
• First Posted: March 10, 2025
• Study Start: July 1, 2025
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 10, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share