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).

Inclusion Criteria:

• Men or women less than or equal to (>=) 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

Exclusion Criteria:

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

• Significant cardiovascular disease within 6 months of starting study therapy
• Active infection requiring antibiotics within 7 days of study treatment.
• 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
• 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

Medications

• 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

• Participants with laboratory values indicating inadequate hematology, hepatic, or renal function

Diagnostic Assessments

• Clinically significant abnormalities in rhythm, conduction, or morphology of resting ECG
• Baseline QT interval corrected for heart rate using Fridericia's formula (QTcF) >=470 msec
• 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
• 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
• Active HBV infection. Participants with resolved infection or who are on Stable antiviral therapy are eligible
• Active HCV infection. Participants who have completed definitive antiviral therapy with post treatment confirmation of eradication are eligible