BI 3706674 for Stomach and Esophageal Cancer

Not currently recruiting at 24 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must not be taking: Chemotherapy, Hormonal, Immunotherapy, others

Disqualifiers: Uncontrolled hypertension, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: up to 3.5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to determine the optimal dose of a new treatment, BI 3706674, for individuals with advanced stomach or esophageal cancer. Researchers are evaluating whether this drug, which blocks growth signals, can shrink tumors. Suitable candidates for this trial have stomach or esophageal cancer unresponsive to other treatments and possess a specific genetic profile (KRAS wild type). Participants will take the treatment in tablet form and attend regular visits to monitor their health and any side effects. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial requires that you stop taking any previous anti-cancer chemotherapy at least 3 weeks before starting the trial drug, and any anti-cancer hormonal treatment or immunotherapy at least 2 weeks before. The protocol does not specify about other medications, so it's best to discuss with the trial team.

Is there any evidence suggesting that BI 3706674 is likely to be safe for humans?

Research has shown that BI 3706674 was tested in animals, where it was well-tolerated and helped shrink tumors. In these tests, the treatment proved more effective with the right dose.

However, this study marked the first time BI 3706674 was tested in humans, so limited safety information might be available. The study aimed to find the best dose that people with advanced stomach or esophageal cancer could handle. Doctors closely monitored participants for side effects and overall health during the trial.

Since this study was in its early phase, it focused on determining the treatment's safety and optimal dose. Early human trials like this one are crucial for understanding potential side effects and how well people tolerate new treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for stomach and esophageal cancer, such as chemotherapy and radiation, aim to kill cancer cells directly but often affect healthy cells too. Researchers are excited about BI 3706674 because it targets specific pathways involved in cancer cell growth, potentially minimizing damage to healthy cells. This precision approach could lead to fewer side effects and improved effectiveness compared to current options. Additionally, the dose escalation and expansion phases might allow for personalized treatment adjustments, offering hope for better patient outcomes.

What evidence suggests that BI 3706674 might be an effective treatment for stomach and esophageal cancer?

Research has shown that BI 3706674 may help treat stomach and esophageal cancers. In lab studies using human cancer models, BI 3706674 blocked signals that promote tumor growth, causing them to shrink. The treatment was generally well-tolerated, with effects varying based on the dose. This trial will explore BI 3706674 in different phases: Part A (Phase Ia) for dose escalation, Part B (Phase Ib) for dose confirmation, and Part C (Phase Ib) for dose expansion. Although these findings are early, they offer hope that this treatment could benefit people with advanced cancer when other treatments have not been successful. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

Adults with advanced stomach or oesophagus cancer who have not had success with previous treatments, or for whom no other treatment options are available. They must have a specific type of genetic feature in their cancer cells (KRAS wild type amplification) and be able to undergo certain biopsies if needed. Participants should be generally healthy otherwise, with a life expectancy of at least 3 months.

Inclusion Criteria

I have at least one cancer lesion that can be measured and hasn't been just radiated.

My side effects from previous cancer treatments are mild, except for hair loss and nerve issues.

Life expectancy ≥3 months at the start of treatment in the opinion of the investigator.

Exclusion Criteria

Left ventricular ejection fraction (LVEF) <50%.

I have been treated with drugs targeting RAS, MAPKs, or SOS1.

I haven't had cancer treatment in the last 3 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants take BI 3706674 as a tablet with different doses tested to find a suitable dose that can be tolerated

up to 3.5 years

Regular visits to the study site

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BI 3706674

Trial Overview The trial is testing different doses of BI 3706674, an experimental drug taken as a tablet that may block tumor growth by interfering with growth signals. The goal is to determine the highest dose patients can tolerate without severe side effects and to see if it can shrink tumors.

How Is the Trial Designed?

Group I: Part C (Phase Ib): Dose expansion Experimental Treatment 1 Intervention

Group II: Part B (Phase Ib): Dose confirmation Experimental Treatment 1 Intervention

Group III: Part A (Phase Ia): Dose escalation Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

Paclitaxel demonstrated significant effectiveness against esophageal cancer in a phase II trial, indicating its potential as a treatment option for this type of cancer.

Irinotecan has proven to be effective as a single-agent treatment for both gastric and colorectal cancers, while docetaxel showed notable activity in advanced gastric cancer and a 29% response rate in pancreatic cancer, highlighting its versatility in treating various cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New systemic drugs in the treatment of gastrointestinal cancer. Ogawa, M.[2019]

In a multicenter phase IB/II trial involving 28 patients with locally advanced esophageal cancer, adding cetuximab to preoperative chemoradiotherapy was found to be safe, with no treatment-related mortality and a high rate of complete or near complete pathologic regression (68%).

The study demonstrated that the combination therapy did not increase postoperative complications, as 86% of patients completed the treatment and R0 resection was achieved in 25 patients, indicating promising efficacy for further investigation in phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab in combination with chemoradiotherapy before surgery in patients with resectable, locally advanced esophageal carcinoma: a prospective, multicenter phase IB/II Trial (SAKK 75/06). Ruhstaller, T., Pless, M., Dietrich, D., et al.[2018]

Biologic therapies, particularly those targeting HER2 and VEGF, are showing promise in treating esophageal and gastric cancers, with trastuzumab and ramucirumab currently recommended by the NCCN for specific patient groups.

Recent studies indicate that other agents like pertuzumab, apatinib, and pembrolizumab may improve overall and progression-free survival, suggesting a growing role for targeted biologic therapies in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. Samson, P., Lockhart, AC.[2020]

In a study of 202 patients with HER2-negative advanced esophagogastric cancer, the platinum-based therapy FOLFOX demonstrated significantly better progression-free survival (PFS) compared to the non-platinum regimen IT, with median PFS of 5.7 months versus 2.9 months.

Most patients (86%) had low ERCC1 levels (< 1.7), and for this group, FOLFOX was also more effective than IT in terms of PFS and response rate, indicating that ERCC1 levels did not significantly alter the treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Phase II Study Prospectively Evaluating Treatment of Metastatic Esophageal, Gastric, or Gastroesophageal Cancer by Gene Expression of ERCC1: SWOG S1201. Iqbal, S., McDonough, S., Lenz, HJ., et al.[2021]

The combination of everolimus with standard mFOLFOX6 chemotherapy in patients with metastatic gastroesophageal adenocarcinoma showed a manageable safety profile, with common grade 3 toxicities including mucositis and neutropenia, and dose-limiting toxicities primarily related to treatment delays.

This treatment regimen demonstrated significant efficacy, with 83% of patients experiencing a partial response, and median overall survival and progression-free survival rates of 20.3 and 14.5 months, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Trial of mFOLFOX6 and Everolimus (NSC-733504) in Patients with Metastatic Gastroesophageal Adenocarcinoma. Chung, V., Frankel, P., Lim, D., et al.[2016]

Citations

1. mskcc.org mskcc.org/cancer-care/clinical-trials/24-027

A Phase 1 Study of BI 3706674 in People With Gastric and ... Researchers in this study want to find the best dose of BI 3706674 to use in people with stomach or esophagus cancers.

2. aacrjournals.org aacrjournals.org/cancerres/article/84/6_Supplement/3317/739110/Abstract-3317-KRASmulti-inhibitor-BI-3706674-shows

Abstract 3317: KRASmulti inhibitor BI 3706674 shows efficacy ... In vivo, BI 3706674 was well-tolerated and showed dose-dependent efficacy in cell line-derived and patient-derived xenograft models of human ...

3. withpower.com withpower.com/trial/phase-1-solid-tumor-kras-mutation-9-2023-10803

BI 3706674 for Stomach and Esophageal Cancer Paclitaxel demonstrated significant effectiveness against esophageal cancer in a phase II trial, indicating its potential as a treatment option for this type of ...

4. mayo.edu mayo.edu/research/clinical-trials/cls-20564175

A Study to Test How Well Different Doses of BI 3706674 ... The purpose of this study is to find a suitable dose of BI 3706674 that people with advanced cancer can tolerate when taken alone, and to check ...

5. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2023-0574.html

2023-0574: Open-label dose-finding trial to explore safety, ... The purpose of this study is to find a suitable dose of BI 3706674 that people with advanced cancer can tolerate when taken alone. Another purpose is to check ...

6. mayo.edu mayo.edu/research/clinical-trials/diseases-conditions/stomach-cancer

Stomach Cancer Clinical Trials The purpose of this study is to find a suitable dose of BI 3706674 that people with advanced cancer can tolerate when taken alone, and to check whether BI ...