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

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).

Drug: PT0511. Intravenous infusion.

Drug: Cetuximab. Intravenous infusion.

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.

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.

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.

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.

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.

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.

Number of Participants with Dose-limiting Toxicities (DLT). Time frame: Cycle 1 (Cycle length=21 days).

Number of Participants with Treatment-Emergent Adverse Events (TEAEs). Time frame: Up to 24 months.

Number of Participants with TEAEs Leading to Treatment Interruptions, Dose Reductions and Permanent Discontinuations. Time frame: Up to 24 months.

Cmax/C0: Maximum Blood Concentration (Cmax) and/or Concentration at Time 0 (C0) of PT0511. Time frame: 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. Time frame: 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. Time frame: 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. Time frame: 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. Time frame: Cycle 1 Days 1 and 15: Pre-infusion and up to 24 hours post-infusion (Cycle length=21 days).

CL: Clearance of PT0511. Time frame: Cycle 1 Days 1 and 15: Pre-infusion and up to 24 hours post-infusion (Cycle length=21 days).

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 …

Enrollment: 210 participants (estimated).