Solid Tumor, KRAS mutations, NSCLC, CRC, PDAC
Conditions
Interventions
This study will be in 2 parts:
Part 1: 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 hav
their cancer gets worse
they start other cancer treatment
or they ask to stop study treatment.
People will visit the clinic on certain days during their study treatment, with extra visits during the first 2 cycles of study treatment.
People will visit the c
Sponsors
Dario Ruscica
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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. 2. 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. a. For the ASP5834 monotherapy dose expansion part, the following criteria apply: - Pancreatic ductal adenocarcinoma (PDAC) Expansion Cohort(s) o Participant has histologically confirmed locally advanced (unresectable) or metastatic PDAC. o Participant has a documented KRAS G12V, G12D, G12C, G12R, G12A or G13D mutation determined by local testing. o 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. o 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). o 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) o Participant has histologically confirmed locally advanced (unresectable) or metastatic NSCLC. o Participant has a documented KRAS G12V, G12D, G12R, G12A or G13D mutation determined by local testing. o 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. o 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). o 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 o Participant has a histologically confirmed locally advanced (unresectabl
Exclusion criteria
Exclusion criteria: 1. Participant has symptomatic or untreated central nervous system (CNS) metastases. Participants with stable, asymptomatic and treated CNS metastases are eligible. 2. Participant has leptomeningeal disease as a manifestation of the current malignancy. 3. 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. 4. 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. 5. 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. 6. 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. 7. Resting heart rate < 50 bpm at screening, unless clinically appropriate (e.g., well-conditioned participant) and deemed not clinically significant. 8. Known family history of sudden cardiac death before 50 years of age. 9. Hypokalemia that is not corrected to within the institutional normal range prior to first dose of study intervention. 10. 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. 11.Participant has had major surgery within 4 weeks prior to first dose of study intervention. 12.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. 13. Participant has received any radiotherapy (including stereotactic radiosurgery) within 14 days prior to the first dose of study intervention. 14. 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. 15. Participant has an active infection requiring any systemic anti-infectious agents within 14 days prior to study intervention. 16. Participant is expected to require another form of anticancer therapy while on study treatment. 17. Participant requires treatment with concomitant drugs that are strong o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Dose Limiting Toxicities (DLTs) - AEs - Serious AEs (SAEs) - Laboratory test results - Eye examination - ECG - Vital signs - ECHO or MUGA scan assessments - Physical Examination - ECOG performance status scores | — |
Secondary
| Measure | Time frame |
|---|---|
| - Objective Response Rate (ORR), Duration of Response (DOR), and Disease Control Rate (DCR) per RECIST v1.1 - Progression Free Survival (PFS) per RECIST v1.1 - Overall Survival (OS) - Pharmacokinetic parameters of ASP5834 o Area under the concentration-time curve (AUC) at 24 hours (AUC24h) o AUC at 168 hours (AUC168h) (AUC at 336 hours [AUC336h] for once every 2 weeks) o Maximum concentration (Cmax) o Trough concentration (Ctrough) o Terminal elimination half-life (t1/2) o Time of maximum concentration (tmax) - Change from baseline in KRAS protein levels | — |
Countries
France, Japan, Spain, United Status
Contacts
Public ContactInformation Center Medical
Astellas Pharma Inc.
Outcome results
None listed