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

NCT06797336 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PT0253-101
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Solid Tumor

Keywords

KRAS

Outcome Measures

Primary Outcomes (3)

• Number of Participants with Dose-limiting Toxicities (DLT)

  Cycle 1 (Cycle length=21 days)

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

  Up to 24 months

• Number of Participants with TEAEs Leading to Treatment Interruptions, Dose Reductions and Permanent Discontinuations

  Up to 24 months

Secondary Outcomes (11)

• Cmax/C0: Maximum Blood Concentration (Cmax) and/or Concentration at Time 0 (C0) of PT0253

  Cycle 1 Days 1 and 15: Pre-infusion and up to 24 hours post-infusion (Cycle length=21 days)

• Tmax: Time to Reach Cmax of PT0253

  Cycle 1 Days 1 and 15: Pre-infusion and up to 24 hours post-infusion (Cycle length=21 days)

• AUC0-t: Area Under the Curve From time 0 to the time of the Last Quantifiable Concentration of PT0253

  Cycle 1 Days 1 and 15: Pre-infusion and up to 24 hours post-infusion (Cycle length=21 days)

• t1/2: Terminal Elimination Half-life of PT0253

  Cycle 1 Days 1 and 15: Pre-infusion and up to 24 hours post-infusion (Cycle length=21 days)

• AUC0-∞: Area Under the Curve From Time 0 Extrapolated to Infinity of PT0253

  Cycle 1 Days 1 and 15: Pre-infusion and up to 24 hours post-infusion (Cycle length=21 days)

Study Arms (4)

Part 1a, Dose Escalation

EXPERIMENTAL

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

Drug: PT0253

Part 1b, Dose Expansion: Tumor type 1

EXPERIMENTAL

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.

Drug: PT0253

Part 1b, Dose Expansion: Tumor type 2

EXPERIMENTAL

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.

Drug: PT0253

Part 1b, Dose Expansion: Tumor type 3

EXPERIMENTAL

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.

Drug: PT0253

Interventions

PT0253 DRUG

PT0253 injection.

Part 1a, Dose Escalation; Part 1b, Dose Expansion: Tumor type 1; Part 1b, Dose Expansion: Tumor type 2; Part 1b, Dose Expansion: Tumor type 3

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed advanced or metastatic solid malignancy
• 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.
• Measurable disease (RECIST 1.1 Criteria).
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
• Willingness to avoid pregnancy or fathering children from screening through 90 days after the last dose of study treatment.

You may not qualify if:

• 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.
• 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.
• Concurrent participation in another interventional clinical study.
• 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.
• Significant cardiovascular disease within 6 months of starting study therapy.
• Active infection requiring antibiotics within 1 day of study treatment.
• 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.
• Known history of drug-induced liver injury; primary biliary cirrhosis; or ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver, or portal hypertension.
• Major surgery within 4 weeks of the start of study therapy or postoperative complications preventing the participant from adhering to protocol assessments and procedures.
• Known hypersensitivity to any of the products to be administered during dosing.
• 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.
• 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.
• Use of multidrug and toxin extrusion protein 1 (MATE) or MATE2-K substrates that cannot be discontinued prior to the start of study treatment.

Sponsors & Collaborators

• PAQ Therapeutics, Inc.: lead

Study Sites (7)

Dana Farber/Massachusetts General Hospital, Inc

Boston, Massachusetts, 02215, United States

RECRUITING

SCRI Lake Mary

Nashville, Tennessee, 37203, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

New Experimental Therapeutics of San Antonio LLC

San Antonio, Texas, 78229, United States

RECRUITING

START - South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

RECRUITING

START Mountain Region

West Valley City, Utah, 84119, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Central Study Contacts

PAQ Therapeutics

CONTACT

781-819-2949; ClinicalTrials@paqtx.com

Study Design

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

Study Record Dates

• First Submitted: January 22, 2025
• First Posted: January 28, 2025
• Study Start: December 19, 2024
• Primary Completion (Estimated): December 15, 2026
• Study Completion (Estimated): June 16, 2027
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (7)