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

NCT07300150 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PT0511-101
• Study Type: interventional
• Target: 195
• Locations: 1 country
• Sites: 5

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

Conditions

Non-Small Cell Lung Cancer; Solid Tumor; Colorectal Cancer; Pancreatic Cancer

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 (12)

• Cmax/C0: Maximum Blood Concentration (Cmax) and/or Concentration at Time 0 (C0) of PT0511

  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 PT0511

  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 PT0511

  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 PT0511

  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 PT0511

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

Study Arms (9)

Part 1a: Dose Escalation

EXPERIMENTAL

Participants with solid tumors with any KRAS mutation or amplified WT KRAS will receive PT0511 infusion, intravenously (IV), until disease progression or intolerance.

Drug: PT0511

Part 1b: Dose Expansion: Tumor type 1

EXPERIMENTAL

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.

Drug: PT0511

Part 1b: Dose Expansion: Tumor type 2

EXPERIMENTAL

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.

Drug: PT0511; Drug: Cetuximab

Part 1b: Dose Expansion: Tumor type 3

EXPERIMENTAL

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.

Drug: PT0511

Part 1b: Dose Expansion: Tumor type 4

EXPERIMENTAL

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.

Drug: PT0511

Part 1b: Dose Expansion: Tumor type 5

EXPERIMENTAL

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.

Drug: PT0511

Part 1b: Dose Expansion: Tumor type 6

EXPERIMENTAL

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.

Drug: PT0511

Part 1b: Dose Expansion: Tumor type 7

EXPERIMENTAL

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.

Drug: PT0511

Part 1b: Dose Expansion: Tumor type 8

EXPERIMENTAL

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.

Drug: PT0511

Interventions

PT0511 DRUG

Intravenous infusion.

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; Part 1b: Dose Expansion: Tumor type 4; Part 1b: Dose Expansion: Tumor type 5; Part 1b: Dose Expansion: Tumor type 6; Part 1b: Dose Expansion: Tumor type 7; Part 1b: Dose Expansion: Tumor type 8

Cetuximab DRUG

Intravenous infusion.

Part 1b: Dose Expansion: Tumor type 2

Eligibility Criteria

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

You may qualify if:

• Men or women \>=18 years of age
• Histologically or cytologically confirmed advanced or metastatic solid malignancy.
• 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.
• Measurable disease (RECIST 1.1 Criteria).
• ECOG Performance Status 0 or 1.
• Willingness to avoid pregnancy or fathering children screening through 90 days after the last dose of study treatment.

You may not qualify if:

• Cancer History
• 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.
• 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
• 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.
• Concurrent participation in another interventional clinical study.
• 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
• Prior treatment with a KRAS/RAS degrader.
• Medical History

Sponsors & Collaborators

• PAQ Therapeutics, Inc.: lead

Study Sites (5)

Dana-Farber/Massachusetts General Hospital, Inc

Boston, Massachusetts, 02215, 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

MeSH Terms

Conditions

Colorectal Neoplasms; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: December 10, 2025
• First Posted: December 23, 2025
• Study Start: November 21, 2025
• Primary Completion (Estimated): October 18, 2028
• Study Completion (Estimated): October 18, 2028
• Last Updated: May 7, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (5)