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

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.
• •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.