BI 3706674 for Stomach and Esophageal Cancer

Recruiting at16 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Boehringer Ingelheim

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

Disqualifiers: Uncontrolled hypertension, Heart failure, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial is for adults with advanced stomach or oesophagus cancer who have no other treatment options. It tests a new drug, BI 3706674, taken as a tablet, to find an appropriate amount and see if it can shrink tumors by blocking their growth signals. Participants will have periodic health monitoring to track their health and any side effects.

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.

What data supports the effectiveness of the drug BI 3706674 for stomach and esophageal cancer?

The research mentions that biologic therapies, which include targeted treatments like those affecting HER2 and VEGF, have shown promise in increasing survival rates for esophageal and gastric cancers. Although BI 3706674 is not specifically mentioned, similar targeted therapies have been effective in treating these types of cancers. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• BI 3706674 (Monoclonal Antibodies)

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

Biologic therapy in esophageal and gastric malignancies: current therapies and future directions. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. United States 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. [2021]

4. United States 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). [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Phase Ib Trial of mFOLFOX6 and Everolimus (NSC-733504) in Patients with Metastatic Gastroesophageal Adenocarcinoma. [2016]