Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
Inclusion Criteria:
1. Patients with pathologically confirmed diagnosis of locally advanced or metastatic
gastric adenocarcinoma (GAC), oesophageal adenocarcinomas (EAC), and gastroesophageal
junction adenocarcinoma (GEJAC) with Kirsten rat sarcoma viral oncogene homolog (KRAS)
wild type (wt) amplification and documented disease progression despite at least 1
line of prior therapy. KRAS status will be confirmed retrospectively for those with a
known KRAS status or determined prospectively (dose confirmation and expansion) if
KRAS status is unknown, using archival tissue (if available) or a fresh biopsy.
Dose escalation (Part A) only: Patients with advanced or metastatic relapsed or
refractory solid tumours of any histology with KRAS wt amplification or harbouring a
KRAS G12V mutation who have exhausted treatment options known to prolong survival for
their disease. Detection of KRAS status by a local test is allowed for enrolment but
will be retrospectively confirmed.
2. Patients who have failed conventional treatment or for whom no therapy of proven
efficacy exists or who are not eligible for established treatment options.
3. Dose confirmation (Part B) only: Patient is willing and able to undergo mandatory pre-
and on-treatment low risk tumour biopsies. Patients with a high risk for biopsy
complications can be included without undergoing pre- and on-treatment tumour biopsy
as long as archival tumour tissue is available for confirmation of KRAS status.
4. At least one target lesion that can be measured per RECIST version 1.1 (radiated
lesions do not qualify as target lesions unless there has been demonstrated
progression of the lesion after completion of radiotherapy) Dose escalation (Part A)
only: Patients with no lesions measurable per RECIST version 1.1 may be included if
agreed between Sponsor and investigator.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. All toxicities related to previous anti-cancer therapies have resolved ≤ CTCAE Grade 1
prior to trial treatment administration (except for alopecia and peripheral neuropathy
which must be ≤ CTCAE Grade 2 and amenorrhea/menstrual disorders which can be any
grade).
7. Life expectancy ≥3 months at the start of treatment in the opinion of the investigator.
8. Age ≥18 years of age, or over the legal age of consent as required by local
legislation.
Exclusion Criteria:
1. Previous anti-cancer chemotherapy within 3 weeks of the first administration of trial
drug.
2. Previous anti-cancer hormonal treatment or anti-cancer immunotherapy within 2 weeks of
the first administration of trial drug.
3. Previous treatment with rat sarcoma (RAS), mitogen-activated protein kinases (MAPKs)
or son of sevenless homolog 1 (SOS1) targeting agents.
4. Presence of cardiovascular abnormalities such as uncontrolled hypertension (defined as
systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥90 millimetre of mercury
(mmHg)), congestive heart failure New York Heart Association (NYHA) classification of
≥ III or IV, unstable angina or poorly controlled arrhythmia. History of myocardial
infarction, stroke, or pulmonary embolism within 6 months prior to randomisation.
5. Left ventricular ejection fraction (LVEF) < 50%.
6. Congenital or family history of long QT prolongation syndrome.
7. Mean resting corrected QT interval (QTcF) > 470 msec.
8. Radiotherapy within 2 weeks prior to start of treatment, except as follows:
- Palliative radiotherapy to regions other than the chest is allowed if completed
at least 2 weeks prior to randomisation.
- Single dose palliative radiotherapy for symptomatic metastasis within 2 weeks
prior to randomisation may be allowed but must be discussed with the Sponsor.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 10/11/23. Questions regarding updates should be directed to the study team contact.