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A Phase 1 Study of ASP5834 in Participants with Locally Advanced (Unresectable) or Metastatic Solid Tumor Malignancies with KRAS Mutations or KRAS Amplifications

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

Dario Ruscica

Astellas Pharma Inc.

2-5-1, Nihonbashi-Honcho, Chuo-ku, Tokyo

clinicaltrialregistration@astellas.com

Medical Information Center

Astellas Pharma Inc.

2-5-1, Nihonbashi-Honcho, Chuo-ku, Tokyo

+81-120-189-371

clinicaltrialregistration@astellas.com

Recruiting

Mar. 30, 2026

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

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 (unresectable) or metastatic solid tumor type other than PDAC, colorectal cancer (CRC) or NSCLC.
o Participant has a documented KRAS G12V, G12D, G12C, G12R, G12A or G13D mutation or KRAS amplification (copy number >=4) determined by local testing.
o 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.

b. For ASP5834 combination therapy dose escalation and dose expansion parts, the following criteria apply:
- CRC Dose Escalation and Dose Expansion Parts
o Participant has histologically confirmed locally advanced (unresectable) or metastatic adenocarcinoma of the colon or rectum.
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 fluoropyrimidine, oxaliplatin, irinotecan and anti-vascular endothelial growth factor (VEGF) therapy or is ineligible for these therapies.
o 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.
o Participant with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) CRC must have also received prior treatment with immune checkpoint inhibitors or is ineligible for these therapies.
3. 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.
4. 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.
5. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. 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.
7. 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).
8. Female participant:
- Is not pregnant confirmed by pregnancy test and medical evaluation by interview, and at least 1 of the following conditions apply:
a. Not a woman of childbearing potential (WOCBP)
b. 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.
- Must not be breastfeeding or lactating starting at screening and throughout the investigational period and for 6 months after final investigational study intervention administration.
- 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.
(Due to character limitation, please see the remaining criteria in the other attachment #1)

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 or moderate inhibitors or inducers of Cytochrome P450 family 3 subfamily A (CYP3A).
18. Participant has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to the start of study intervention.
19. Participant has any condition that makes the participant unsuitable for study participation.
20. Participant has a known or suspected hypersensitivity to the protocol specified study intervention(s) or any components of the formulation used.
21. Participant has a corrected QT interval by Fridericia (QTcF) value (single electrocardiogram [ECG]) of > 450 msec (men) or > 470 msec (women) during screening.
22. Participant has a left ventricular ejection fraction (LVEF) < 50% as assessed by echocardiogram (ECHO) (or multigated acquisition (MUGA)) performed at screening.
23. 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.
24. 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.
25. For ASP5834 combination therapy (dose escalation and expansion parts), the following criteria apply:
- Participant had prior discontinuation of panitumumab treatment due to toxicity or intolerance of panitumumab.

Both

Solid Tumor, KRAS mutations, NSCLC, CRC, PDAC

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 have colorectal cancer will receive ASP5834 with panitumumab. People with any type of solid tumor will receive ASP5834 by itself.
Part 2: Dose Expansion
Other different small groups of people will receive ASP5834 or ASP5834 with panitumumab. They will receive the most suitable doses worked out from Part 1.
In both parts of the study, the study treatments ASP5834 and panitumumab will be given through a vein. This is called an infusion. Each study treatment cycle is either 21 days or 28 days long. People will continue study treatment until: they have medical problems from the study treatment they can't tolerate; 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 clinic shortly after stopping treatment for a health check. The number of visits and checks done will depend on the health of each person and whether they completed their study treatment or not. It is expected that people will be in this study for about 1 year.

- 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

- 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 from the time of dosing to 24 h after dosing (AUC24h)
o Area under the concentration-time curve from the time of dosing to 168 h after dosing (AUC168h) (Area under the concentration-time curve from the time of dosing to 336 h after dosing [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

Mar. 11, 2026

Yes

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/. Study-related supporting documentation is redacted and provided if available, such as the protocol and amendments, statistical analysis plan and clinical study report. Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data. Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

United Status/France/Spain/South Korea