A Study of PT0253 in Participants With KRAS G12D Mutated Advanced Solid Tumors

NCT ID: NCT06797336

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

115 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-19

Study Completion Date

2027-06-16

Brief Summary

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The primary purpose of this study is to evaluate the safety and tolerability, determine the maximally tolerated dose (MTD) and/or recommended Phase 2 dose(s) (RP2D) of PT0253 in adult participants with Kirsten rat sarcoma viral oncogene homolog (KRAS) G12D mutated advanced solid tumors as monotherapy.

Detailed Description

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Conditions

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Solid Tumor

Keywords

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KRAS

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1a, Dose Escalation

Participants with any type of solid tumor will receive PT0253 injection, intravenously (IV) until disease progression or intolerance.

Group Type EXPERIMENTAL

PT0253

Intervention Type DRUG

PT0253 injection.

Part 1b, Dose Expansion: Tumor type 1

Participants with a previously treated tumor type will receive PT0253 injection until disease progression or intolerance. Recommended dose or doses for expansion for Part 1b will be determined based on the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) data for PT0253 established in Part 1a.

Group Type EXPERIMENTAL

PT0253

Intervention Type DRUG

PT0253 injection.

Part 1b, Dose Expansion: Tumor type 2

Participants with a previously treated tumor type will receive PT0253 injection until disease progression or intolerance. Recommended dose or doses for expansion for Part 1b will be determined based on the safety, tolerability, PK and PD data for PT0253 established in Part 1a.

Group Type EXPERIMENTAL

PT0253

Intervention Type DRUG

PT0253 injection.

Part 1b, Dose Expansion: Tumor type 3

Participants with a previously treated tumor type will receive PT0253 injection until disease progression or intolerance. Recommended dose or doses for expansion for Part 1b will be determined based on the safety, tolerability, PK and PD data for PT0253 established in Part 1a.

Group Type EXPERIMENTAL

PT0253

Intervention Type DRUG

PT0253 injection.

Interventions

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PT0253

PT0253 injection.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Histologically or cytologically confirmed advanced or metastatic solid malignancy
2. Participant has a pathologically documented, locally advanced or metastatic malignancy with KRAS p.G12D mutation identified through molecular testing using a validated institutional or commercial test.
3. Measurable disease (RECIST 1.1 Criteria).
4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
5. Willingness to avoid pregnancy or fathering children from screening through 90 days after the last dose of study treatment.

Exclusion Criteria

1. Active brain metastasis or carcinomatous meningitis. If participants have had brain metastases resected or have received radiation therapy, they may be eligible if: (1) study treatment begins at least 4 weeks from the end of brain-specific therapy, (2) residual neurological symptoms Grade less than or equal to (\<=) 2, (3) currently on stable doses of corticosteroids, and (4) pre-study brain magnetic resonance imaging (MRI) documents no new/worsening brain lesions.
2. History of any other malignancy within the past 2 years, except:

* Malignancy treated with curative intent and with no known active disease present \>=2 years before enrolment and felt to be at low risk for recurrence by the investigator
* Basal or squamous cell carcinoma of the skin, in situ cervical cancer, early -stage endometrial cancer that has been definitively treated, superficial bladder cancer, Gleason 6/7 treated prostate cancer, and ductal carcinoma in situ or lobular carcinoma in situ of the breast.
4. Concurrent participation in another interventional clinical study.
5. Treatment with anticancer medications or investigational drugs within 14-28 days or 5 half-lives (whichever is longer) before the first administration of study drug. Concurrent hormonal therapy for prostate or breast cancer is allowed.
6. Significant cardiovascular disease within 6 months of starting study therapy.
7. Active infection requiring antibiotics within 1 day of study treatment.
8. Known HIV infection with a cluster of differentiation 4+ (CD4+) T-cell count less than (\<) 200 cells per microliter \[/mcL\] and/or a detectable viral load per parameters of assay and/or on an anti-retroviral regimen containing a strong or moderate cytochrome (CY)P3A4/5 inhibitor or inducer and/or on a new anti-retroviral regimen for less than 28 days prior to the initiation of study treatment.
9. Known history of drug-induced liver injury; primary biliary cirrhosis; or ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver, or portal hypertension.
10. Major surgery within 4 weeks of the start of study therapy or postoperative complications preventing the participant from adhering to protocol assessments and procedures.
11. Known hypersensitivity to any of the products to be administered during dosing.
12. Any disease or disorder that, in the opinion of the investigator, may compromise the ability of the participant to provide written informed consent and/or to comply with all required study procedures.
13. Part 1a (Dose escalation): Use of a strong or moderate CYP3A4/5 inhibitor or inducer, strong P-glycoprotein (P-gp) inhibitor or inducer or P-gp substrate.
14. Use of multidrug and toxin extrusion protein 1 (MATE) or MATE2-K substrates that cannot be discontinued prior to the start of study treatment.
15. Participants with laboratory values indicating inadequate hematology, hepatic, or renal function.
16. Clinically significant abnormalities in rhythm, conduction, or morphology of resting electrocardiogram (ECG) or baseline QT interval corrected for heart rate using Fridericia's formula (QTcF) \>=450 milliseconds (msec).
17. Female participants who are pregnant or lactating/breast feeding or who plan to breastfeed while on study through 28 days after receiving the last dose of study drug.
18. Active hepatitis B virus (HBV) infection. Participants with resolved infection or who are on stable antiviral therapy are eligible.
19. Active hepatitis C virus (HCV) infection. Participants who have completed definitive antiviral therapy with post treatment confirmation of eradication are eligible.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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PAQ Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Dana Farber/Massachusetts General Hospital, Inc

Boston, Massachusetts, United States

Site Status RECRUITING

SCRI Lake Mary

Nashville, Tennessee, United States

Site Status RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, United States

Site Status RECRUITING

New Experimental Therapeutics of San Antonio LLC

San Antonio, Texas, United States

Site Status RECRUITING

START - South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, United States

Site Status RECRUITING

START Mountain Region

West Valley City, Utah, United States

Site Status RECRUITING

NEXT Virginia

Fairfax, Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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PAQ Therapeutics

Role: CONTACT

Phone: 781-819-2949

Email: [email protected]

Facility Contacts

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Role: primary

Alexander Philipovskiy

Role: primary

Vivek Subbiah

Role: primary

Role: primary

Role: primary

Role: primary

Role: primary

Other Identifiers

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PT0253-101

Identifier Type: -

Identifier Source: org_study_id