Conditions

• Gastric Cancer
• Gastroesophageal Junction Cancer

Eligibility

Eligible Ages

Over 18 Years

Eligible Sex

All

Accepts Healthy Volunteers

No

Criteria

Inclusion

1. Sign and date the Tissue Prescreening ICF, prior to HER2 and PD-L1 CPS central
testing. Sign and date the Main Screening ICF, prior to the start of any
trial-specific qualification procedures. Sign and date the Optional PGx ICF
(included in the Main Screening ICF) prior to any PGx procedure.

2. Adults ≥18 years of age on the day of signing the ICF. Follow local regulatory
requirements if the legal age of consent for trial participation is >18 years old.

3. Previously untreated, unresectable, locally advanced or metastatic gastric or GEJ
adenocarcinoma histologically confirmed by pathology report. Prior treatment in the
perioperative and/or adjuvant setting is permissible, provided there is >6 months
between the end of perioperative or neoadjuvant treatment and the diagnosis of
recurrent disease.

Note: Prior use of IO (ie, anti-PD-1/PD-L1) therapy in the (neo)adjuvant setting is
allowed as long as there is >6 months between the end of IO therapy and the
diagnosis of recurrent disease.

4. Centrally determined HER2-positive (IHC 3+ or IHC 2+/ISH-positive) gastric or GEJ
cancer as classified by the American Society of Clinical Oncology-College of
American Pathologists for GC on a tumor biopsy as detected by prospective central
test on new (core, incisional, excisional biopsy) or existing tumor tissue taken at
the time of diagnosis of locally advanced or metastatic disease.

Note: Archival samples taken from a previous diagnostic or surgical biopsy not
previously irradiated can be accepted. Details pertaining to tumor tissue submission
can be found in the Study Laboratory Manual.

5. All participants must provide a tumor sample for tissue-based IHC staining to
centrally determine HER2 expression, PD-L1 CPS, and other correlatives. The
mandatory FFPE tumor sample can be from either the primary tumor or metastatic
biopsy. Specimens with limited tumor content (as centrally determined) and cytology
samples are inadequate for defining tumor HER2 and PD-L1 status.

6. At least 1 target measurable lesion on CT or MRI, assessed by the investigator based
on RECIST v1.1. Lesions situated in a previously irradiated area are considered
measurable if progression has been shown in such lesions.

7. LVEF ≥50% within 28 days before randomization.

exclusion criteria

1. Prior exposure to other HER2-targeting therapies (including ADCs).

2. Lack of physiological integrity of the upper gastrointestinal tract (ie, severe
Crohn disease that results in malabsorption) or malabsorption syndrome that would
preclude feasibility of oral chemotherapy (ie, capecitabine).

3. Known DPD enzyme deficiency. Note: Screening for DPD enzyme deficiency is required
only in regions/countries where DPD testing is SoC and with unknown DPD status. For
regions/countries where DPD testing is not SoC, local practice should be followed.

4. Contraindications to trastuzumab, 5-FU, capecitabine, cisplatin, or oxaliplatin
treatment as per local label.

5. Medical history of myocardial infarction within 6 months before randomization or
symptomatic CHF (New York Heart Association Class II to IV). Participants with
troponin levels above ULN at Screening (as defined by the manufacturer) and without
any myocardial infarction -related symptoms should have a cardiologic consultation
during the Screening Period to rule out myocardial infarction.

6. Has a corrected QT interval (QTcF) prolongation to >470 ms (females) or >450 ms
(males) based on the average of the screening triplicate 12-lead ECG.

7. Has a history of (non-infectious) ILD/pneumonitis that required steroids, has
current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by
imaging at Screening

8. Lung-specific intercurrent clinically significant illnesses including, but not
limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months
of the trial randomization, severe asthma, severe chronic obstructive pulmonary
disease, restrictive lung disease, pleural effusion, etc).

Recruiting Locations

Study Contact