A Study of PT0511 in Participants With KRAS Mutated or Amplified Advanced Solid Tumors

NCT ID: NCT07300150

Last Updated: 2025-12-23

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

195 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-11-21

Study Completion Date

2028-10-18

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 PT0511 in adult participants with solid tumors as monotherapy and in combination with cetuximab in participants with colorectal cancer (CRC).

Detailed Description

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Conditions

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Colorectal Cancer Pancreatic Cancer Non-Small Cell Lung Cancer 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 solid tumors with any KRAS mutation or amplified WT KRAS will receive PT0511 infusion, intravenously (IV), until disease progression or intolerance.

Group Type EXPERIMENTAL

PT0511

Intervention Type DRUG

Intravenous infusion.

Part 1b: Dose Expansion: Tumor type 1

Participants with tumor type 1 will receive PT0511 infusion 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 PT0511 established in Part 1a.

Group Type EXPERIMENTAL

PT0511

Intervention Type DRUG

Intravenous infusion.

Part 1b: Dose Expansion: Tumor type 2

Participants with tumor type 2 will receive PT0511 infusion in combination with cetuximab infusion, 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 PT0511 established in Part 1a.

Group Type EXPERIMENTAL

PT0511

Intervention Type DRUG

Intravenous infusion.

Cetuximab

Intervention Type DRUG

Intravenous infusion.

Part 1b: Dose Expansion: Tumor type 3

Participants with tumor type 3 will receive PT0511 infusion 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 PT0511 established in Part 1a.

Group Type EXPERIMENTAL

PT0511

Intervention Type DRUG

Intravenous infusion.

Part 1b: Dose Expansion: Tumor type 4

Participants with tumor type 4 will receive PT0511 infusion 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 PT0511 established in Part 1a.

Group Type EXPERIMENTAL

PT0511

Intervention Type DRUG

Intravenous infusion.

Part 1b: Dose Expansion: Tumor type 5

Participants with tumor type 5 will receive PT0511 infusion 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 PT0511 established in Part 1a.

Group Type EXPERIMENTAL

PT0511

Intervention Type DRUG

Intravenous infusion.

Part 1b: Dose Expansion: Tumor type 6

Participants with tumor type 6 will receive PT0511 infusion 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 PT0511 established in Part 1a.

Group Type EXPERIMENTAL

PT0511

Intervention Type DRUG

Intravenous infusion.

Part 1b: Dose Expansion: Tumor type 7

Participants with tumor type 7 will receive PT0511 infusion 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 PT0511 established in Part 1a.

Group Type EXPERIMENTAL

PT0511

Intervention Type DRUG

Intravenous infusion.

Part 1b: Dose Expansion: Tumor type 8

Participants with tumor type 8 will receive PT0511 infusion 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 PT0511 established in Part 1a.

Group Type EXPERIMENTAL

PT0511

Intervention Type DRUG

Intravenous infusion.

Interventions

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PT0511

Intravenous infusion.

Intervention Type DRUG

Cetuximab

Intravenous infusion.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Men or women \>=18 years of age
2. Histologically or cytologically confirmed advanced or metastatic solid malignancy.
3. Participant has a pathologically documented, locally advanced or metastatic malignancy with any KRAS mutation or wild-type (WT) KRAS amplification identified through molecular testing using a Clinical Laboratory Improvement Amendments (CLIA) certified, validated institutional or commercial test.

• Participant must have received at least 1 and no more than 4 prior systemic therapies or be intolerant or ineligible for available therapies known to provide clinical benefit.
4. Measurable disease (RECIST 1.1 Criteria).
5. ECOG Performance Status 0 or 1.
6. Willingness to avoid pregnancy or fathering children screening through 90 days after the last dose of study treatment.

Exclusion Criteria

Cancer History

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 \<=2, (3) currently on stable doses of corticosteroids, and (4) pre-study brain 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.

Prior Cancer Therapy
3. Unresolved toxicities from prior anti-cancer therapies. Participants with prior endocrine replacement therapies are eligible for entry even if administered to treat endocrine deficiency due to the prior anti-cancer therapy.
4. Concurrent participation in another interventional clinical study.
5. Treatment with anticancer medications or investigational drugs within the following intervals before the first administration of study drug:

* At least 14 days for chemotherapy or targeted small-molecule therapy.
* At least 28 days for a prior monoclonal antibody.
* At least 28 days or 5 half-lives (whichever is longer) for all other investigational study drugs or devices. For drugs with very long half-lives, participants may be allowed to enroll prior to 5 half-lives at the discretion of the investigator in discussion with the medical monitor.
* Note: Concurrent hormonal therapy for prostate or breast cancer is allowable
6. Prior treatment with a KRAS/RAS degrader.

Medical History
7. Significant cardiovascular disease within 6 months of starting study therapy.
8. Active infection requiring antibiotics within 7 days of study treatment.
9. Known HIV infection with a CD4+ T-cell count \<200 cells/mcL and/or a detectable viral load per parameters of assay and/or on an anti-retroviral regimen containing a strong or moderate CYP3A4/5 inhibitor or inducer and/or on a new anti-retroviral regimen for less than 28 days prior to the initiation of study treatment.
10. Known history of drug-induced liver injury; primary biliary cirrhosis; or ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver, or portal hypertension.
11. Major surgery within 4 weeks of the start of study therapy or postoperative complications preventing the participant from adhering to protocol assessments and procedures.
12. Known hypersensitivity to any of the products to be administered during dosing.
13. 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.

Medications
14. Part 1a (Dose escalation): Use of a strong or moderate CYP3A4/5 inhibitor or inducer, Use of a strong P-gp inhibitor or inducer.

Organ Function
15. Participants with laboratory values indicating inadequate hematology, hepatic, or renal function.

Diagnostic Assessments
16. Clinically significant abnormalities in rhythm, conduction, or morphology of resting ECG.
17. Baseline QT interval corrected for heart rate using Fridericia's formula (QTcF) \>=470 msec
18. Female participants of childbearing age with a positive urine or serum test within 7 days of study start or confirmation from Ob/Gyn that any positive bHCG test is not representative of an ongoing pregnancy.
19. Women who are lactating/breast feeding or who plan to breastfeed while on study through 28 days after receiving the last dose of study drug.
20. Active HBV infection. Participants with resolved infection or who are on Stable antiviral therapy are eligible.
21. Active 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 NOT_YET_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 NOT_YET_RECRUITING

START Mountain Region

West Valley City, Utah, United States

Site Status NOT_YET_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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Leon Pappas

Role: primary

Ildefonso Ismael Rodriguez Rivera

Role: primary

Drew Rasco

Role: primary

William McKean

Role: primary

Alexander Spira

Role: primary

Other Identifiers

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PT0511-101

Identifier Type: -

Identifier Source: org_study_id