A Study to Find a Suitable Dose of ASP5834 in Adults With Solid Tumors

Genes contain genetic code which tell the body which proteins to make. Many types of cancer are caused by changes, or mutations, in a gene called KRAS. Researchers are looking for ways to stop the actions of abnormal proteins made from the mutated KRAS gene. ASP5834 is being studied in people with solid tumors who have certain KRAS gene mutations. Some people with solid tumors of the colon or rectum (colorectal cancer), will be given ASP5834 with panitumumab. Panitumumab is a treatment for colorectal cancer. In this study, the researchers will learn how ASP5834 is processed by and acts upon the body. This information will help find a suitable dose of ASP5834 and check for any potential medical problems from the treatment. The main aims of this study are to check the safety of ASP5834 given by itself or given with panitumumab, and how well it is tolerated; and to find a suitable dose of ASP5834 given by itself or given with panitumumab. People in this study will be adults with locally advanced, unresectable, or metastatic solid tumors with certain KRAS gene mutations. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. They either haven't responded to standard treatment or couldn't be given standard treatment. The key reasons people cannot take part are if they have specific uncontrollable cancers such as symptomatic or untreated cancers in nervous system, have specific heart conditions, swelling and irritation of lung tissues (pneumonitis or interstitial lung disease, also called ILD), infections, or have recently had a stroke or a bleed on the brain. In this study, ASP5834 is being given to humans for the first time. This is an open-label study. This means that people in this study and clinic staff will know that they will receive ASP5834 by itself or ASP5834 with panitumumab. This study will be in 2 parts: Part 1 is called Dose Escalation. Different small groups of people will receive lower to higher doses of either: ASP5834 by itself or ASP5834 with panitumumab. Only people who have colorectal cancer will receive ASP5834 with panitumumab. People with any type of solid tumor will receive ASP5834 by itself. For each dose, all medical problems will be recorded. A medical expert panel will check the results and decide if the next group can receive a higher dose of ASP5834. The panel will do this until the planned maximum …

Drug: ASP5834. Intravenous infusion

Drug: panitumumab. Intravenous infusion

ASP5834 Dose Escalation (experimental): Participants will receive sequential doses levels of ASP5834 intravenously following 1 of 2 dose regimens.

ASP5834 Dose Expansion (Tumor/ Mutation Specific) (experimental): Participants with select tumor types will receive 1 of 2 dose regimens of ASP5834 with dose level(s) selected from dose escalation.

ASP5834 Dose Expansion (Dose-ranging) (experimental): Participants will receive dose level(s) and regimen of ASP5834 based on emerging data from Dose Escalation alone or Dose Escalation and Dose Expansion cohorts.

ASP5834 combination therapy Dose Escalation (experimental): Participants will receive sequential doses levels of ASP5834 intravenously following 1 of 2 dose regimens based on emerging data. Panitumumab will be administered every 2 weeks.

ASP5834 monotherapy therapy Dose Expansion (experimental): Participants will receive 1 of 2 dose regimens of ASP5834.

ASP5834 combination therapy Dose Expansion (experimental): Participants will receive ASP5834 and panitumumab with dose level(s) and regimen selected from dose escalation (Combination Therapy). Panitumumab will be administered every 2 weeks.

Incidence of Dose Limiting Toxicities (DLTs) (Dose Escalation only). A DLT is defined as any Adverse Event (AE) which meets DLT criteria, not clearly due to the underlying disease or extraneous causes, that occurs within the DLT observation period. Time frame: Up to 21 days.

Number of participants with Adverse Events (AEs). An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. This includes events related to the comparator, if applicable, and events related to the (study) procedures. Time frame: Up to 40 months.

Number of Participants with Serious Adverse Events (SAEs). An SAE is any untoward medical occurrence that at any dose either results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or other medical situation. Time frame: Up to 40 months.

Number of participants with laboratory value abnormalities and/or adverse events (AEs). Number of participants with potentially clinically significant laboratory values. Time frame: Up to 40 months.

Number of Participants with Eye Exam abnormalities and/or Adverse Events (AEs). Number of participants with potentially clinically significant eye exam values. Time frame: Up to 39 months.

Objective Response Rate (ORR) of ASP5834 per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Time frame: Up to 45 months.

Duration of Response (DOR) of ASP5834 per RECIST v1.1. Time frame: Up to 45 months.

Disease Control Rate (DCR) of ASP5834 per RECIST v1.1. Time frame: Up to 45 months.

Progression Free Survival (PFS) per RECIST v1.1. Time frame: Up to 45 months.

Overall Survival (OS). Time frame: Up to 45 months.

Pharmacokinetics (PK) of ASP5834 in plasma: area under the concentration-time curve from the time of dosing to 24 hours after dosing (AUC24h). Time frame: Up to 39 months.

Inclusion Criteria: * Participant has histologically confirmed locally advanced (unresectable) or metastatic solid tumor malignancy with a documented Kirsten rat sarcoma viral oncogene homolog (KRAS) G12V, G12D, G12C, G12R, G12A or G13D mutation or KRAS amplification (copy number \>/= 4) determined by local testing. * For a participant with a documented KRAS amplification, only those with no other co-occurring KRAS mutation or those with a co-occurring KRAS G12V, G12D, G12C, G12R, G12A or G13D mutation are eligible. * Unique to Europe (EU): Only participants who have pre-existing local results can be enrolled. * For the ASP5834 monotherapy dose escalation part, participant with any histologically confirmed locally advanced (unresectable) or metastatic solid tumor malignancy is eligible. Participant must have received prior standard therapy in the advanced setting, and the investigator does not see any further clinical benefit from continuing such therapy or the participant is ineligible to receive standard approved therapies. * For the ASP5834 monotherapy dose expansion part, the following criteria apply: * \[pancreatic ductal adenocarcinoma (PDAC) Expansion Cohort(s)\] Participant has histologically confirmed locally advanced (unresectable) or metastatic PDAC. * \[PDAC Expansion Cohort(s)\] Participant has a documented KRAS G12V, G12D, G12C, G12R, G12A or G13D mutation determined by local testing. * \[PDAC Expansion Cohort(s)\] Participant must have received standard therapy in the advanced setting, including prior therapy with a gemcitabine-based or fluoropyrimidine-based regimen or is ineligible for these therapies. * \[PDAC Expansion Cohort(s)\] No more than 2 prior lines of systemic therapy are allowed in the advanced setting (note: maintenance therapy does not count as a separate line of therapy). * \[PDAC Expansion Cohort(s)\] For a participant who received prior neoadjuvant or adjuvant chemotherapy and had recurrence on or within 6 months of completion of therapy, the neoadjuvant or adjuvant chemotherapy should be counted as a regimen in the advanced setting. * \[non-small cell lung cancer (NSCLC) Expansion Cohort(s)\] Participant has histologically confirmed locally advanced (unresectable) or metastatic NSCLC. * \[NSCLC Expansion Cohort(s)\] Participant has a documented KRAS G12V, G12D, G12R, G12A or G13D mutation determined by local testing. * \[NSCLC Expansion Cohort(s)\] Participant must have received standard therapy in the advanced setting, …

Enrollment: 404 participants (estimated).