PT0511 for advanced solid tumors with KRAS mutations or amplifications

A Phase 1, Open-label Dose Escalation and Expansion Study OF PT0511 in Participants With KRAS Mutated OR Amplified Advanced Solid Tumors

This trial tests whether the drug PT0511, given alone or with cetuximab for colorectal cancer, is safe and tolerable in adults with advanced solid tumors that have KRAS mutations or KRAS amplification.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 195 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: PAQ Therapeutics, Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation, cetuximab
• Locations: 5 sites (Boston, Massachusetts and 4 other locations)
• Trial ID: NCT07300150 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, dose-escalation trial of PT0511 as monotherapy for adults with advanced or metastatic solid tumors harboring KRAS mutations or KRAS amplification, with a combination arm of PT0511 plus cetuximab specifically for colorectal cancer. The primary objectives are to characterize safety, determine the maximally tolerated dose (MTD) and define recommended Phase 2 dose(s) using sequential dose cohorts. Key eligibility includes adults (≥18) with measurable disease per RECIST 1.1, ECOG 0–1, and 1–4 prior systemic therapies or intolerance/ineligibility to standard options. The trial is sponsored by PAQ Therapeutics and is open at sites in Boston and San Antonio.

Who should consider this trial

Good fit: Adults (≥18) with advanced or metastatic solid tumors that have documented KRAS mutations or KRAS amplification, measurable disease, ECOG performance status 0–1, and who have received 1–4 prior systemic therapies are the intended candidates.

Not a fit: Patients with active brain metastases or carcinomatous meningitis, ECOG >1, more than four prior systemic therapies, or without KRAS mutation/amplification are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, PT0511 could offer a new targeted option for patients with KRAS-mutated or KRAS-amplified tumors, including colorectal cancers that no longer respond to existing therapies.

How similar studies have performed: KRAS-targeted therapies have shown promise in certain KRAS alterations, and cetuximab is effective in KRAS wild-type colorectal cancer, but combining a KRAS-directed agent with cetuximab is an emerging strategy with limited published clinical data to date.

Eligibility criteria

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.

Where this trial is running

Boston, Massachusetts and 4 other locations

• Dana-Farber/Massachusetts General Hospital, Inc — Boston, Massachusetts, United States (Recruiting)
• New Experimental Therapeutics of San Antonio LLC — San Antonio, Texas, United States (Recruiting)
• START - South Texas Accelerated Research Therapeutics, LLC — San Antonio, Texas, United States (Recruiting)
• START Mountain Region — West Valley City, Utah, United States (Recruiting)
• NEXT Virginia — Fairfax, Virginia, United States (Recruiting)

Study contacts

• Study coordinator: PAQ Therapeutics

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