Testing a new drug for advanced stomach and esophagus cancer

Open-label Dose-finding Trial to Explore Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of BI 3706674 Given Orally as Monotherapy in Patients With Unresectable Metastatic KRAS Wild Type Amplified Gastric, Oesophageal, and Gastroesophagealjunction Adenocarcinoma

This study is testing a new pill for adults with advanced stomach and esophagus cancer who haven't had success with other treatments to see if it can shrink their tumors and how much of the drug they can safely take.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 146 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Boehringer Ingelheim (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 17 sites (Phoenix, Arizona and 16 other locations)
• Trial ID: NCT06056024 on ClinicalTrials.gov

What this trial studies

This study involves adults with advanced cancer in the stomach and esophagus who have not responded to previous treatments or have no existing treatment options. Participants will receive a new drug, BI 3706674, which is being tested for the first time in humans to determine the appropriate dosage that can be tolerated. The study aims to assess the drug's ability to shrink tumors by blocking growth signals. Participants will take the drug in tablet form and will have regular visits to monitor their response and any side effects.

Who should consider this trial

Good fit: Ideal candidates are adults with advanced gastric or esophageal adenocarcinoma who have exhausted prior treatment options.

Not a fit: Patients with early-stage cancer or those who have not yet undergone any treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced stomach and esophagus cancer.

How similar studies have performed: Other studies have shown promise with similar approaches targeting KRAS mutations, but this specific drug is being tested for the first time.

Eligibility criteria

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.

Further inclusion criteria apply.

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.

Further exclusion criteria apply.

Where this trial is running

Phoenix, Arizona and 16 other locations

• Mayo Clinic-Arizona — Phoenix, Arizona, United States (Recruiting)
• Yale Cancer Center — New Haven, Connecticut, United States (Recruiting)
• Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)
• Memorial Sloan-Kettering Cancer Center — New York, New York, United States (Recruiting)
• University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• National Cancer Center Hospital East — Chiba, Kashiwa, Japan (Recruiting)
• Japanese Foundation for Cancer Research — Tokyo, Koto-ku, Japan (Recruiting)
• Seoul National University Bundang Hospital — Seongnam, Korea, Republic of (Recruiting)
• Seoul National University Hospital — Seoul, Korea, Republic of (Recruiting)
• Severance Hospital — Seoul, Korea, Republic of (Recruiting)
• Asan Medical Center — Seoul, Korea, Republic of (Recruiting)
• Samsung Medical Center — Seoul, Korea, Republic of (Recruiting)
• The Catholic University of Korea, Seoul St.Mary's Hospital — Seoul, Korea, Republic of (Not_yet_recruiting)
• Ajou University Hospital — Suwon, Korea, Republic of (Not_yet_recruiting)
• Nckuh — Tainan, Taiwan (Recruiting)
• National Taiwan University Hospital — Taipei, Taiwan (Recruiting)

Study contacts

• Study coordinator: Boehringer Ingelheim

Conditions Solid Tumor, KRAS Mutation