Informations générales (source: ClinicalTrials.gov)
A Phase 1 Study of ASP5834 in Participants With Locally Advanced (Unresectable) or Metastatic Solid Tumor Malignancies With KRAS Mutations or KRAS Amplifications
Interventional
Phase 1
Astellas Pharma Inc (Voir sur ClinicalTrials)
juillet 2025
avril 2029
01 septembre 2026
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 number
of people are treated or until suitable doses have been selected for Part 2.
Part 2 is called 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. The study doctors will check for any
medical problems from ASP5834. Also, people in the study will have a health check. On
some visits they will also have scans to check for any changes in their cancer. Tumor
samples will be taken at certain visits during study treatment with the option of a tumor
sample being taken if people's cancer gets worse or the cancer comes back.
People will visit the clinic shortly after stopping treatment for a health check. After
this, people will have health checks every couple of months to check the condition of
their cancer. 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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Fabrice BARLESI | 31/08/2026 13:45:09 | Contacter | ||
Critères
Tous
- 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.