EIS-12656 for Solid Tumors

Overseen By Adrian Schomburg

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Eisbach Bio GmbH

Disqualifiers: Gastrointestinal disease, Cardiovascular disease, Brain metastases, others

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

Compensation: Varies

Number of Visits: Unknown

144 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, EIS-12656, for individuals with advanced solid tumors that have specific genetic mutations. The study examines the drug's safety and effectiveness, both alone and with other drugs like Trastuzumab deruxtecan and Olaparib. It targets those who have tried other treatments without success or cannot undergo standard therapies. Ideal participants have a type of solid tumor that has recurred or spread and possess a specific gene mutation affecting DNA repair. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial group, offering participants a chance to be among the first to benefit from this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that EIS-12656 might be safe for individuals with certain solid tumors. One study found that this drug could effectively treat many challenging tumors with fewer side effects than some current treatments, suggesting it may be well-tolerated by patients.

EIS-12656 is also being tested with two other drugs, Olaparib and Trastuzumab deruxtecan (T-DXd). Olaparib is already used in some cancer treatments, so its safety is well-established. T-DXd has demonstrated safety in real-world use, although more research is needed to confirm this over the long term.

Overall, evidence suggests these treatments could be promising in terms of safety. However, since EIS-12656 is still in early testing, more data is needed to be certain. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about EIS-12656 because it offers a novel approach to treating solid tumors. Unlike traditional chemotherapy, which targets all rapidly dividing cells, EIS-12656 is designed to work more precisely, potentially leading to fewer side effects. In combination treatments, like with Trastuzumab deruxtecan (T-DXd) and Olaparib, EIS-12656 aims to enhance the efficacy of these drugs. This multi-faceted strategy could provide a more effective and tailored treatment option for patients, setting it apart from existing therapies.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Research has shown that EIS-12656 may help treat advanced solid tumors by blocking a specific enzyme called ALC1, which aids cancer cell growth. Early studies suggest it might effectively shrink tumors, particularly those with certain genetic changes. In this trial, some participants will receive EIS-12656 with Olaparib, potentially enhancing the effectiveness of this existing cancer drug. Others will receive EIS-12656 with Trastuzumab deruxtecan, a treatment known for its success in HER2-positive cancers, potentially improving results. These combinations aim to target tumor cells more precisely and improve patient outcomes. ^{1 2 3 5 6}

Who Is on the Research Team?

Timothy Yap

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with advanced solid tumors that have certain genetic mutations. Participants should be adults who can take oral medication and have measurable disease per specific criteria. They must not have had prior treatments that would interfere with the study.

Inclusion Criteria

Measurable disease (RECIST 1.1 Criteria)

My condition worsened after previous treatments or I couldn't tolerate them.

Life expectancy greater than 3 months

Exclusion Criteria

I have a significant gastrointestinal condition.

I have not had radiation therapy in the last 2 weeks.

I have a serious heart condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive ascending doses of EIS-12656 to evaluate safety and tolerability and determine an effective dose for Phase 2

3 weeks

Multiple visits for dose escalation monitoring

Dose Expansion

Participants receive EIS-12656 monotherapy or in combination with a PARPi or T-DXd to evaluate safety, tolerability, and anti-tumor activity

6 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

45 days

What Are the Treatments Tested in This Trial?

Interventions

• EIS-12656

Trial Overview The trial is testing EIS-12656, a new drug, alone and in combination with Trastuzumab deruxtecan or Olaparib. It has two parts: first to find the right dose (Phase 1) and then to see how well it works at that dose (Phase 2).

How Is the Trial Designed?

Group I: EIS-12656 Dose Escalation Experimental Treatment 1 Intervention

Group II: Dose Expansion Module 3 (EIS-12656 + T-DXd) Experimental Treatment 2 Interventions

EIS-12656 will be given in combination with Trastuzumab deruxtecan

Group III: Dose Expansion Module 2 (EIS-12656 + Olaparib) Experimental Treatment 2 Interventions

EIS-12656 will be given in combination with Olaparib

Group IV: Dose Expansion Module 1 (EIS-12656 Monotherapy) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Eisbach Bio GmbH

Lead Sponsor

Trials

1

Recruited

140+

Published Research Related to This Trial

In a study involving 12 HER2-negative metastatic breast cancer patients, re-administration of the chemotherapy drug eribulin after a cycle of S-1 resulted in a progression-free survival (PFS) of 13 weeks, extending the total PFS to 30 weeks.

The safety profile of eribulin re-administration was consistent with previous studies, indicating that it can be safely used again in patients who have not progressed after initial treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Exploratory Phase II Study of Eribulin Re-challenge After Short Term Therapy of 5-Fluorouracil for HER2 Negative, Advanced or Recurrent Breast Cancer. Takashima, T., Nishimura, S., Kawajiri, H., et al.[2021]

In two phase 3 studies involving 1864 women with advanced metastatic breast cancer, the development of new metastases was linked to a significantly higher risk of death, highlighting the severity of this progression event.

Eribulin treatment showed a longer time to new metastasis or death compared to the comparator in one study, and it resulted in significantly better overall survival for patients with new metastases in that same study, suggesting its potential effectiveness in this specific subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"New" metastases are associated with a poorer prognosis than growth of pre-existing metastases in patients with metastatic breast cancer treated with chemotherapy. Twelves, C., Cortes, J., Kaufman, PA., et al.[2018]

Eribulin, used as a single agent in 31 patients with advanced or recurrent breast cancer, showed a response rate of 22.5% and a disease control rate of 80.6%, indicating its potential efficacy in this challenging patient population.

The study suggests that prolonging the duration of eribulin treatment may be more crucial for improving overall survival than the relative dose intensity, highlighting its unique mechanism of action compared to traditional chemotherapy drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Eribulin Administration Methods to Extend the Survival Time of Patients with Advanced or Recurrent Breast Cancer, Consideringthe Relative Dose Intensity, Time to Treatment Failure, Pretreatment Regimen Number, and Tumor Subtype]. Sunagawa, Y., Mizuno, Y.[2018]

Eribulin mesylate (Halaven) was approved by the FDA for treating refractory metastatic breast cancer based on a study of 762 patients, showing a significant increase in overall survival (OS) of 13.1 months compared to 10.6 months for the control group.

While eribulin improved overall survival, it did not significantly affect progression-free survival, suggesting that OS should be prioritized as a primary endpoint in future clinical trials for advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eribulin mesylate for the treatment of patients with refractory metastatic breast cancer: use of a "physician's choice" control arm in a randomized approval trial. Donoghue, M., Lemery, SJ., Yuan, W., et al.[2016]

In a study of 32 women with advanced or metastatic breast cancer treated with eribulin, the objective response rate was 15.6% and the clinical benefit rate was 31.3%, indicating some level of efficacy in this heavily pretreated population.

The study found that higher relative dose intensity (RDI) of eribulin was associated with better overall survival (OS) and post-progression survival (PPS), while the most common severe side effect was neutropenia, affecting 56% of patients, but no severe peripheral sensory neuropathy was reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment Out Come of Eribulin in Patients with Advanced or Metastatic Breast Cancer Who Resistant to Anthracycline and Taxane]. Tanaka, N., Ogura, K., Hattori, A., et al.[2018]

A meta-analysis of 28 randomized controlled trials involving 17,800 patients revealed that EGFR tyrosine kinase inhibitors (EGFR-TKIs) are associated with a significant risk of adverse events (AEs), with common side effects including diarrhea (53.7%), rash (48.6%), and mucositis (46.5%).

The study highlighted that serious AEs occurred in 18.2% of patients, with treatment discontinuation due to AEs at 12.36%, emphasizing the need for early detection and management of these side effects to improve patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse event profiles of epidermal growth factor receptor-tyrosine kinase inhibitors in cancer patients: A systematic review and meta-analysis. Yin, X., Zhao, Z., Yin, Y., et al.[2023]

A survey of 195 patients and 120 physicians revealed that skin toxicities from EGFR inhibitors are seen as the most discouraging side effect during cancer treatment, impacting quality of life and causing pain.

Despite the negative effects of skin toxicities, 71% of patients were willing to accept them for the sake of more effective cancer therapies, indicating a significant difference in risk tolerance compared to physicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A survey of patient and physician acceptance of skin toxicities from anti-epidermal growth factor receptor therapies. Tischer, B., Bilang, M., Kraemer, M., et al.[2019]

In a study of 274 EGFR mutated non-small cell lung cancer patients with bone metastases, 28% experienced major skeletal related adverse events (SREs), with bone fractures being the most common (20%).

SREs were more likely to occur within the first 12 months of starting tyrosine kinase inhibitors (TKIs), highlighting the need for early intervention with bone resorption inhibitors to potentially reduce these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High Prevalence and Early Occurrence of Skeletal Complications in EGFR Mutated NSCLC Patients With Bone Metastases. Laganà, M., Gurizzan, C., Roca, E., et al.[2022]

In a Phase II study involving 58 patients with metastatic breast cancer who had previously been treated with taxanes and anthracyclines, gefitinib showed limited efficacy, with only 1.7% of patients achieving a partial tumor response.

Despite the low response rate, gefitinib was well tolerated, with side effects consistent with known profiles, and no correlation was found between EGFR expression and treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicentre phase II study on gefitinib in taxane- and anthracycline-pretreated metastatic breast cancer. von Minckwitz, G., Jonat, W., Fasching, P., et al.[2021]

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) significantly enhance progression-free and overall survival in patients with non-small cell lung cancer (NSCLC) who have activating mutations in the EGFR gene.

Despite their efficacy, EGFR-TKIs can cause several adverse events, such as diarrhea, liver toxicity, and skin issues, which can negatively impact patients' quality of life and adherence to treatment; therefore, managing these side effects is crucial for effective therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of EGFR-TKIs for EGFR mutation-positive non-small cell lung cancer. Zhou, JY., Liu, SY., Wu, YL.[2021]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-06470

EIS-12656 as Single Agent and in Combination in Patients ... This trial investigates a new drug, EIS-12656, in participants with specified advanced solid tumors carrying pre-specified mutations.

2. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2024-0131.html

A Phase 1/2, open label trial to investigate the safety, ... This trial investigates a new drug, EIS-12656, in participants with specified advanced solid tumors carrying pre-specified mutations.

3. targetedonc.com targetedonc.com/view/fda-clears-ind-for-eis-12656-a-novel-therapy-for-multiple-solid-tumors

FDA Clears IND for EIS-12656, a Novel Therapy ... The FDA has cleared the IND application for EIS-12656, a first-in-class allosteric inhibitor of ALC1, for the treatment of patients with various solid tumors.

4. synapse.patsnap.com synapse.patsnap.com/drug/49e39bbdede64fa8b327da9abd090de6

EIS-12656 - Drug Targets, Indications, Patents Following IND approval in May 2024, EIS-12656 is currently being assessed as a monotherapy against HRD-positive tumours in the Phase I/II MATCH trial, and ...

5. clinconnect.io clinconnect.io/trials/NCT06525298

EIS-12656 as Single Agent and in Combination in Patients This clinical trial is studying a new drug called EIS-12656 to see how well it works on patients with specific advanced solid tumors that have certain genetic ...

6. smartpatients.com smartpatients.com/trials/NCT06525298

EIS-12656 as Single Agent and in Combination ... This trial investigates a new drug, EIS-12656, in participants with specified advanced solid tumors carrying pre-specified mutations.