New drug targets KRAS mutations in advanced cancers

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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, including prior platinum-based chemotherapy and checkpoint inhibitor therapy or is ineligible for these therapies. Participants with known actionable genomic alterations (AGA) must have received prior therapy with an approved targeted therapy in accordance with local requirements. * \[NSCLC Expansion Cohort(s)\] For a participant who has received prior neoadjuvant or adjuvant therapy and had recurrence during or within 6 months of completion of therapy, the neoadjuvant or adjuvant therapy should be counted as a regimen in the advanced setting (for those who received perioperative therapy, the entire course should be counted as therapy in the advanced setting). * \[NSCLC Expansion Cohort(s)\] For a participant with a history of unresectable Stage III disease who received prior multi-modal therapy and had recurrence on or within 6 months of completion of therapy, the multi-modal therapy should be counted as a therapy in the advanced setting. If chemoradiation was followed by treatment with checkpoint inhibitor therapy without documented progression between chemoradiation and checkpoint inhibitor therapy, the entire treatment course should be counted as therapy in the advanced setting. * \[Other Solid Tumor Expansion Cohort\] Participant has a histologically confirmed locally advanced (unresectable) or metastatic solid tumor type other than PDAC, colorectal cancer (CRC) or NSCLC. * \[Other Solid Tumor Expansion Cohort\] Participant has a documented KRAS G12V, G12D, G12C, G12R, G12A or G13D mutation or KRAS amplification (copy number \>/=4) determined by local testing. * \[Other Solid Tumor Expansion Cohort\] 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 is ineligible to receive standard approved therapies. * For ASP5834 combination therapy dose escalation and dose expansion parts, the following criteria apply: * \[CRC Dose Escalation and Dose Expansion Parts\] Participant has histologically confirmed locally advanced (unresectable) or metastatic adenocarcinoma of the colon or rectum. * \[CRC Dose Escalation and Dose Expansion Parts\] Participant has a documented KRAS G12V, G12D, G12C, G12R, G12A or G13D mutation determined by local testing. * \[CRC Dose Escalation and Dose Expansion Parts\] Participant must have received standard therapy in the advanced setting, including prior therapy with fluoropyrimidine, oxaliplatin and irinotecan and anti-vascular endothelial growth factor (VEGF) therapy or is ineligible for these therapies. * \[CRC Dose Escalation and Dose Expansion Parts\] For a participant who has received neoadjuvant or adjuvant chemotherapy and had recurrence during or within 6 months of completion of therapy, the neoadjuvant or adjuvant chemotherapy should be counted as a regimen in the advanced setting. * \[CRC Dose Escalation and Dose Expansion Parts\] Participant with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC) must have also received prior treatment with immune checkpoint inhibitors or is ineligible for these therapies. * Participant consents to provide tumor specimen in a tissue block or unstained serial slides or a baseline tumor biopsy obtained after the last interventional treatment, but not more than 90 days prior to the start of study intervention. Participant also consents to provide a tumor biopsy during the treatment period as indicated in the schedules of assessments. If a participant cannot provide a tumor specimen or undergo a baseline tumor biopsy procedure no more than 90 days prior to the start of study intervention, contact the medical monitor. Submission of an archival tumor tissue specimen to the central laboratory in addition to the baseline specimen is highly encouraged. * Participant has at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. * Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. * Participant's adverse event (AEs) (excluding alopecia) from prior anti-cancer therapy have improved to Grade 1 or baseline at least 14 days prior to the start of study intervention. Persistent Grade 2 or higher toxicities from prior anti-cancer therapy that are considered clinically irreversible, may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by both the investigator and sponsor. * Participant has adequate organ function as indicated by laboratory values (if a participant has received a recent blood transfusion, the laboratory tests must be obtained \>/= 14 days after any blood transfusion). * Female participant is not pregnant confirmed by pregnancy test and medical evaluation by interview, and at least 1 of the following conditions apply: * Not a woman of childbearing potential (WOCBP) * WOCBP who has a negative urine or serum pregnancy test within 7 days prior to day 1 and agrees to follow the contraceptive guidance from the time of informed consent through at least 6 months after final investigational study intervention administration. * Female participant must not be breastfeeding or lactating starting at screening and throughout the investigational period and for 6 months after final investigational study intervention administration. * Female participant must not donate ova starting at first administration of study intervention and throughout the investigational period and for 6 months after final investigational study intervention administration. * Male participant must agree to use contraception with female partner(s) of childbearing potential (including breastfeeding partner) throughout the treatment period and for 3 months after final investigational study intervention administration. * Male participant must agree to remain abstinent or use a condom with pregnant partner(s) for the duration of the pregnancy throughout the investigational period and for 3 months after final investigational study intervention administration. * Male participant must not donate sperm during the treatment period and for 3 months after final investigational study intervention administration. * Participant agrees not to participate in another interventional study while receiving study intervention in the present study/participating in the present study. Exclusion Criteria: * Participant has symptomatic or untreated central nervous system (CNS) metastases. Participants with stable, asymptomatic and treated CNS metastases are eligible. * Participant has leptomeningeal disease as a manifestation of the current malignancy. * Participant has another prior malignancy active (i.e., requiring treatment or intervention) within the previous 2 years different from the primary malignancy for this study, except for local malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast, which are allowed. * Participant with active hepatitis B (including acute hepatitis B virus (HBV) or chronic HBV) or hepatitis C virus (HCV) (Ribonucleic acid (RNA) detected by qualitative assay). HCV RNA testing is not required in participants with negative HCV antibody testing. * Participant has a known history of human immunodeficiency virus (HIV) infection with Acquired Immune Deficiency Syndrome (AIDS) related complications. No HIV testing is required unless mandated by a local health authority. * Participant has had a myocardial infarction or unstable angina within 6 months prior to the start of study intervention or currently has an uncontrolled illness including, but not limited to symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia (including but not limited to uncontrolled atrial fibrillation, recent restoration of rhythm after atrial fibrillation, clinically significant conduction disorder within 6 months prior to the start of study intervention, or ventricular arrhythmias), obligate use of a cardiac pacemaker, or long QT syndrome. * Resting heart rate \< 50 bpm at screening, unless clinically appropriate (e.g., well-conditioned participant) and deemed not clinically significant. * Known family history of sudden cardiac death before 50 years of age. * Hypokalemia that is not corrected to within the institutional normal range prior to first dose of study intervention. * Participants with clinically significant electrolyte abnormalities (e.g., hypomagnesemia or hypocalcemia) that are not corrected to within the institutional normal range prior to first dose of study intervention. * Participant has had major surgery within 4 weeks prior to first dose of study intervention. * Participant has acute neurological events (e.g., intracranial or subarachnoid hemorrhage, stroke, intracranial trauma) within 6 months prior to the first dose of study intervention. * Participant has received any radiotherapy (including stereotactic radiosurgery) within 14 days prior to the first dose of study intervention. * Participant has received prior KRAS targeting agents (including but not limited to KRAS directed inhibitors, degraders, small interfering RNA \[siRNA\] therapies, vaccines and cellular therapies), with the following exceptions: * In the dose escalation part, a participant with PDAC or NSCLC who has received prior RMC-6236 or RMC-9805 or a participant with NSCLC who has received prior KRAS G12C inhibitors but no other KRAS targeting agents will be eligible. * Participant has an active infection requiring any systemic anti-infectious agents within 14 days prior to study intervention. * Participant is expected to require another form of anticancer therapy while on study treatment. * Participant requires treatment with concomitant drugs that are strong or moderate inhibitors or inducers of Cytochrome P450 family 3 subfamily A (CYP3A). * Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening. * Participant has any condition that makes the participant unsuitable for study participation. * Participant has a known or suspected hypersensitivity to the protocol specified study intervention(s) or any components of the formulation used. * Participant has a corrected QT interval by Fridericia (QTcF) value (single electrocardiogram (ECG)) of \> 450 msec (men) or \> 470 msec (women) during screening. * Participant has a left ventricular ejection fraction (LVEF) \< 50% as assessed by echocardiogram (ECHO) (or multigated acquisition (MUGA)) performed at screening. * Participant with a known history of an acquired KRAS G12V, G12D, G12C, G12R, G12A or G13D mutation or KRAS amplification identified as a resistance mechanism to prior systemic therapy (note: if a participant has more than 1 relevant KRAS alteration \[KRAS G12V, G12D, G12C, G12R, G12A or G13D mutation or KRAS amplification\], only those with a known history of acquired resistance to all relevant KRAS alterations would be excluded). Participant will not be excluded if it is not known whether the KRAS alteration(s) were acquired as a resistance mechanism. * UNIQUE to EU: Participant who is the subject of any legal protection measures under local legislation will not be allowed. * Participant has a history of pneumonitis/interstitial lung disease (ILD) or has current pneumonitis/ILD. Note that a participant with resolved pulmonary infections is eligible. * \[ASP5834 combination therapy\] Participant had prior discontinuation of panitumumab treatment due to toxicity or intolerance of panitumumab.