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

March 4, 2025 updated by: Geode Therapeutics Inc.

A Phase 1 Open-Label, Dose-Escalation and Dose-Expansion Study Evaluating the Safety, Pharmacokinetics and Clinical Activity of Orally Administered GT-220F in Subjects With Metastatic Castration Resistant Prostate Cancer (mCRPC)

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

42

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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.
  2. 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.
  3. Subjects must have received at least one previous AR pathway inhibitor (enzalutamide, apalutamide, darolutamide, abiraterone acetate) for biochemically recurrent or metastatic prostate cancer.
  4. Ongoing ADT with a lutenizing hormone releasing hormone agonist/antagonist or bilateral orchiectomy that results in serum testosterone < 50 ng/dL.
  5. 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).
  6. Subjects must have recovered to grade ≥ 2 or pre-treatment baseline from clinically significant toxic effects of prior therapy.
  7. ECOG performance status >2

  8. Subjects must have adequate organ and marrow function as defined below:

    1. absolute neutrophil count ≥ 1,500/mcL
    2. hemoglobin ≥ 9g/dL
    3. platelets ≥ 75,000/mcL
    4. total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (subjects with Gilbert syndrome are allowed if direct bilirubin within normal limits)
    5. AST(SGOT)/ALT(SGPT) ≤ 3 x institutional ULN
    6. creatinine ≤ 1.5 xULM mg/dL OR a calculated creatinine clearance ≥50mL/min.
  9. Left ventricular ejection fraction at least 50% by echocardiogram or multigated acquisition scan.
  10. Subjects with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, subjects should be class 2B or better.
  11. Men who partner with a woman of childbearing potential must agree to use effective, dual contraceptive methods (i.e., a condom, with female partner using oral, injectable or barrier method) while on study drug and for 4 months afterward.
  12. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Evidence of oncogenic mutations in PIK3CA, RAS or receptor tyrosine kinase (RTK) genes (EGFR, ALK).
  2. Subjects who have had prior treatment with PI3K inhibitors with beta and/or delta isoform activity: GSK2636771, AZD 8186, idelalisib, copanlisib, duvelisib, umbralisib.
  3. Subjects who have had any cancer-directed immunomodulatory or molecularly-targeted agent or monoclonal antibody within 14 days prior to initiation of study drug.
  4. Subjects who have used any investigational agents within 28 days or 5 half-lives from study initiation, whichever is shorter.
  5. 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.
  6. 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.
  7. Subjects who have had major surgery within 28 days prior to registration.
  8. Subjects with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to GT-220F.
  9. Subjects with known human immunodeficiency virus or acquired immunodeficiency syndrome-related illness.
  10. 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.
  11. Pulmonary embolism within 1 month prior to initiation of study drug.
  12. Unstable cardiac dysrhythmias or persistent prolongation of the QTc (Fridericia) interval to >470msec.
  13. Evidence of Grade ≥ 2 intracranial hemorrhage.
  14. 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.
  15. Subjects with uncontrolled intercurrent illness, including active or clinically unstable bacterial, viral or fungal infection requiring systemic therapy.
  16. Subjects with difficulty swallowing/unable to swallow pills; malabsorption syndrome; refractory nausea and vomiting, chronic gastrointestinal (GI) disease or previous significant bowel resection with clinically significant sequelae that would preclude adequate absorption of study drug.
  17. Another cancer for which they are receiving active treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GT-220F Dose Level 1
GT-220F 50mg, oral capsule, once a day
Drug: GT-220F capsule
GT-220F capsule for oral administration
Other Names:
  • 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
Experimental: GT-220F Dose Level 2
GT-220F increased dose level to be determined, oral capsule, once or twice a day
Drug: GT-220F capsule
GT-220F capsule for oral administration
Other Names:
  • 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
Experimental: GT-220F Dose Level 3
GT-220F increased dose level to be determined (if needed), oral capsule, once or twice a day
Drug: GT-220F capsule
GT-220F capsule for oral administration
Other Names:
  • 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
Experimental: GT-220F Dose Level 4
GT-220F increased dose level to be determined (if needed), oral capsule, once or twice a day
Drug: GT-220F capsule
GT-220F capsule for oral administration
Other Names:
  • 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
Experimental: GT-220F Dose Level 5
GT-220F increased dose level to be determined (if needed), oral capsule, once or twice a day
Drug: GT-220F capsule
GT-220F capsule for oral administration
Other Names:
  • 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
Experimental: GT-220F Dose Expansion
GT-220F recommended phase 2 dose, oral capsule, once or twice a day
Drug: GT-220F capsule
GT-220F capsule for oral administration
Other Names:
  • 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Limiting Toxicity (DLT)
Time Frame: at the end of Cycle 1 (each cycle is 28 days)
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)
Time Frame: at the end of Cycle 1 (each cycle is 28 days)
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
Time Frame: at the end of Cycle 1 (each cycle is 28 days)
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
Time Frame: from date of randomization to date of progression, assessed up to 50 weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective tumor response rate (ORR)
Time Frame: from date of randomization to date of progression, assessed up to 50 weeks
The number of subjects achieving objective response [complete response (CR) and partial response (PR)] divided by number of subjects who initiate treatment
from date of randomization to date of progression, assessed up to 50 weeks
Duration of objective tumor response (DOR)
Time Frame: from date of randomization to date of progression, assessed up to 50 weeks
The duration of objective response will be measured from the time measurement criteria are met for complete reponse or partial response (whichever is first recorded) until the first date that recurrent or progressive disease (PD) is documented
from date of randomization to date of progression, assessed up to 50 weeks
Disease control rate (DCR)
Time Frame: from date of randomization to date of progression, assessed up to 50 weeks
The percentage of patients who experience complete response, partial response, or stable disease (SD)
from date of randomization to date of progression, assessed up to 50 weeks
Radiographic progression-free survival (PFS)
Time Frame: from date of randomization to date of progression, assessed up to 50 weeks
Time from treatment initiation to the earlier of (1) disease progression by RECIST1.1 and/or Prostate Cancer Working Group 3 criteria or (2) death due to to any cause.
from date of randomization to date of progression, assessed up to 50 weeks
Prostate specific antigen measurements - change from baseline
Time Frame: from date of randomization to date of progression, assessed up to 50 weeks
Proportion of patients achieving 30%, 50% or 90% reduction in prostate specific antigen (PSA) measurement from baseline.
from date of randomization to date of progression, assessed up to 50 weeks
Area under the curve (AUC)
Time Frame: 22 days from baseline
Pharmacokinetic assessment of area under the curve (AUC) for GT-220F and GT-220F-M1 (active metabolite)
22 days from baseline
Maximum plasma concentration (Cmax)
Time Frame: 22 days from baseline
Pharmacokinetic assessment of maximum plasma concentration (Cmax) for GT-220F and GT-220F-M1 (active metabolite)
22 days from baseline
Trough plasma concentration (Cmin)
Time Frame: 22 days from baseline
Pharmacokinetic assessment of trough plasma concentration (Cmin) for GT-220F and GT-220F-M1 (active metabolite)
22 days from baseline
Time to maximum plasma concentration (Tmax)
Time Frame: 22 days from baseline
Pharmacokinetic assessment of time to maximum plasma concentration (Tmax) for GT-220F and GT-220F-M1 (active metabolite)
22 days from baseline
Plasma half-life (T1/2)
Time Frame: 22 days from baseline
Pharmacokinetic assessment of plasma half-life (T1/2) for GT-220F and GT-220F-M1 (active metabolite)
22 days from baseline
Plasma clearance (CL)
Time Frame: 22 days from baseline
Pharmacokinetic assessment of plasma clearance (CL) for GT-220F and GT-220F-M1 (active metabolite)
22 days from baseline
Volume of distribution
Time Frame: 22 days from baseline
Pharmacokinetic assessment of volume of distribution for GT-220F and GT-220F-M1 (active metabolite)
22 days from baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Geode Therapeutics Inc.

Investigators

  • Principal Investigator: Alok Tewari, MD, PhD, Dana-Farber Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2025

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

February 28, 2025

First Submitted That Met QC Criteria

March 4, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 4, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GT-220F-101

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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