BI 1823911 + BI 1701963 for Cancer

Not currently recruiting at 17 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Boehringer Ingelheim

Must not be taking: Anticancer chemotherapy, Anticancer hormonal

Disqualifiers: Cardiovascular abnormalities, Uncontrolled hypertension, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: up to 39 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for individuals with advanced cancers that have a specific KRAS mutation, which accelerates tumor growth. It tests two medicines, BI 1823911 and BI 1701963, to determine their effectiveness in shrinking these tumors. The goal is to identify the safest and most effective dose of these medicines, either alone or in combination. Suitable candidates have cancers such as lung, colorectal, pancreatic, or bile duct cancer, and previous treatments have been ineffective. Participants will take the medicine daily, with doctors regularly assessing the cancer's response and monitoring any side effects. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive these new medicines.

Will I have to stop taking my current medications?

The trial requires that you stop any previous anticancer chemotherapy at least 3 weeks before starting the trial drug, and any anticancer hormonal treatment or immunotherapy at least 2 weeks before. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BI 1701963 has been tested for safety in patients with advanced cancers that have a KRAS mutation. Studies indicate that patients generally tolerate BI 1701963 well. However, like many new treatments, some patients experienced side effects, which researchers closely monitored.

BI 1823911 is a newer treatment and is being administered to people for the first time in clinical studies. Consequently, there is less information about its safety. The goal is to find a tolerable dose, both when taken alone and with BI 1701963. Researchers are testing the combination of these two treatments to determine if they can effectively stop cancer growth.

While BI 1701963 alone has shown a reasonable safety profile, BI 1823911 remains in the early stages of testing to assess its tolerability. Researchers will carefully monitor participants to track any unwanted effects as they occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments, BI 1823911 and BI 1701963, because they work differently from existing cancer therapies. Unlike traditional treatments like chemotherapy, which target rapidly dividing cells indiscriminately, BI 1701963 targets specific proteins involved in cancer cell growth, potentially leading to fewer side effects. Meanwhile, BI 1823911 offers a new approach by inhibiting pathways that help cancer cells survive. This targeted action could improve effectiveness and reduce harm to healthy cells, making these treatments promising alternatives to current options.

What evidence suggests that these treatments might be effective for cancer?

In this trial, participants will join either a Monotherapy Arm or a Combination Therapy Arm. Studies have shown that BI 1701963, which participants in the Monotherapy Arm may receive, effectively targets KRAS mutations that promote cancer growth. In previous patients, BI 1701963 was well tolerated and controlled the disease for up to 18 weeks. Meanwhile, research on combining BI 1701963 with another treatment, BI 1823911, which participants in the Combination Therapy Arm may receive, has shown promising results. These two treatments worked together in early lab studies, leading to tumor shrinkage in models of non-small cell lung cancer. These findings suggest that these treatments could effectively slow down or reduce tumor growth in people with KRAS mutations. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

Adults with advanced cancers (like lung, colorectal, pancreatic, bile duct) that have a specific KRAS mutation and haven't responded to previous treatments or lack treatment options. They must be relatively healthy (ECOG status of 0 or 1), have certain normal organ function levels, measurable tumors per RECIST criteria, and acceptable blood counts.

Inclusion Criteria

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

My cancer has a specific KRAS G12C mutation.

My cancer is advanced and has been confirmed by tests.

Exclusion Criteria

My heart's pumping ability is below normal.

I haven't taken experimental drugs or targeted therapy within the last 28 days.

I haven't had cancer hormone therapy or immunotherapy in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BI 1823911 alone or in combination with BI 1701963 to determine the maximum tolerated dose and evaluate efficacy

up to 39 months

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• BI 1701963
• BI 1823911

Trial Overview The trial is testing BI 1823911 alone and combined with BI 1701963 in different doses to find the highest tolerable amount for patients. It aims to see if these drugs can shrink tumors in those with a particular KRAS mutation. Participants will take tablets daily as long as they benefit without severe side effects.

How Is the Trial Designed?

Group I: Monotherapy Arm Experimental Treatment 2 Interventions

Each arm consists of three parts (dose escalation (A), dose confirmation (B), and dose expansion (C).

Group II: Combination Therapy Arm Experimental Treatment 2 Interventions

Will be started after confirmation of safety in the Monotherapy Arm. Each arm consists of three parts (dose escalation (A), dose confirmation (B), and dose expansion (C).

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04835714

A Study to Find a Safe and Effective Dose of BI 1701963 ... A KRAS mutation makes cancer grow faster. The study tests 2 medicines called BI 1701963 and BI 3011441. BI 1701963 and BI 3011441 prevent activation of KRAS.

2. aacrjournals.org aacrjournals.org/cancerres/article/80/16_Supplement/1091/640981/Abstract-1091-BI-3406-and-BI-1701963-Potent-and

BI-3406 and BI 1701963: Potent and selective SOS1::KRAS ... Both combinations show strong in vivo efficacy in tumor mouse models. The SOS1::KRAS/MEK inhibitor combination results in anti-tumor effects in ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9394389/

Expanding the Reach of Precision Oncology by Drugging All ... BI 1701963 was generally well tolerated, with the maximum tolerated dose reached at 800 mg, and stable disease up to 18 weeks in 7 of 31 patients with solid ...

4. boehringer-ingelheim.com boehringer-ingelheim.com/us/media/press-releases/boehringer-ingelheim-and-mirati-therapeutics-announce-clinical-collaboration-study-bi-1701963

BI & Mirati Therapeutics To Study KRAS Cancers | BI US BI 1701963 is currently being evaluated in a Phase I clinical trial in patients with advanced KRAS-mutated cancers to evaluate safety, ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2405803324002759

KRAS inhibitors: resistance drivers and combinatorial ... BI 1701963, 1, Solid tumor ... J.K. Lee, et al. Comprehensive pan-cancer genomic landscape of KRAS altered cancers and real-world outcomes in solid tumors.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04975256

Adagrasib in Combination With BI 1701963 in Patients ... This study will evaluate safety, tolerability, drug levels, molecular effects and clinical activity of MRTX849 (adagrasib) in combination with BI 1701963 in ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.TPS3651

A phase I, open-label, dose-escalation trial of BI 1701963 ... A first-in-human trial of BI 1701963 in patients aged ≥18 years with tumors harboring KRAS mutations. Primary objectives are to determine the maximum tolerated ...