EMB-01 for Advanced Cancer

Recruiting at 4 trial locations

Overseen By Xuemei Xie

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Shanghai EpimAb Biotherapeutics Co., Ltd.

Disqualifiers: CNS malignancy, Uncontrolled hypertension, Diabetes, others

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

Compensation: Varies

Number of Visits: 2

Duration: Up to 2 years

186 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test EMB-01, a new treatment for people with advanced or metastatic solid tumors. Researchers seek to determine the safety and effectiveness of EMB-01, particularly for those who have exhausted all standard treatments without success. The study consists of two parts: identifying the optimal dose and then further testing that dose. This trial may suit individuals with advanced cancers, such as lung or colorectal cancer, who have specific genetic markers (like EGFR or cMet changes) and have not responded well to standard treatments. As a Phase 1 trial, this research focuses on understanding how EMB-01 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop any prior anti-tumor treatment at least 4 weeks before starting the study drug, or within 5 half-lives of the medication. Additionally, certain types of radiation therapy must be stopped 2 to 3 weeks before the first dose of EMB-01.

Is there any evidence suggesting that EMB-01 is likely to be safe for humans?

Research has shown that EMB-01 is generally safe, with side effects similar to those from treatments targeting specific proteins called EGFR and cMET. Studies have found that patients, even those who have tried similar treatments, tolerate EMB-01 well. So far, these studies have reported no unexpected or severe safety issues. Although this trial targets individuals with advanced or spreading tumors, earlier research provides some confidence about the treatment's safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about EMB-01 for advanced cancer because it offers a novel approach by combining two mechanisms of action in one treatment. Unlike traditional options that may target only a single pathway, EMB-01 is designed to simultaneously inhibit two key pathways involved in tumor growth and survival. This dual-targeting strategy aims to enhance treatment effectiveness and potentially overcome resistance seen with other therapies. By leveraging this innovative mechanism, EMB-01 holds promise for improving outcomes in patients with advanced cancer.

What evidence suggests that EMB-01 might be an effective treatment for advanced cancer?

Research has shown that EMB-01 is promising for treating advanced cancer. In a study with 29 participants, 24.1% experienced partial tumor shrinkage, and 86.2% had their cancer either halted or reduced. EMB-01 targets two proteins, EGFR and cMET, which can help stop cancer growth. Early results are encouraging, but further research is needed to confirm these findings. Participants in this trial will receive EMB-01 in a dose escalation phase to determine the maximum tolerated dose, followed by an expansion phase at the recommended Phase II dose. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic solid tumors, including NSCLC, who've tried standard treatments without success or can't tolerate them. Phase II specifically requires EGFR mutant/cMET aberration and progression after treatment like osimertinib. Participants need good organ function, an ECOG score of 0-1 (or ≤2 for phase II), and must use contraception if fertile.

Inclusion Criteria

I agreed to molecular pre-screening and have EGFR or cMet abnormalities.

You have advanced or metastatic solid tumors such as lung, colorectal, gastric, or liver cancer and have not responded to standard treatments or cannot access standard treatments. For lung cancer, you have specific genetic mutations and have not responded to certain approved medications. You also need to have normal organ function and have stopped previous treatments for a certain amount of time before starting this study. If you can have children, you need to use birth control during the study. Your overall health score should be good for this study.

Able to understand and willing to sign the Informed Consent Form (ICF).

Exclusion Criteria

I have a primary brain tumor or symptoms from brain metastases.

Molecular Pre-screening Exclusion Criteria (Phase II only): Subject who meets any of the follow criteria can't be proceeded to clinical screening: Patients who are unwilling to sign the molecular pre-screening ICF. Patients for whom local EGFR and/or cMET data or the results of central laboratory testing do not meet the molecular pre-screening inclusion criteria.

Pregnant or nursing females.

Timeline for a Trial Participant

Molecular Pre-screening

Participants undergo molecular pre-screening to determine eligibility based on molecular status

Not specified

Clinical Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive intravenous infusions of EMB-01 weekly in 28-day cycles

Up to 2 years

Weekly visits (in-person)

Safety Follow-up

Participants are monitored for safety 30 days after the last dose

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• EMB-01

Trial Overview EMB-01 is being tested in this first-in-human study to see how it works on various advanced cancers. The trial has two parts: dose escalation to find the safe amount (Phase I) and expansion where more patients get that dose to further assess its effects (Phase II).

How Is the Trial Designed?

Group I: Dose Escalation-Part 1, Expansion-Part 2 Experimental Treatment 1 Intervention

In part 1, escalating dose cohort, patients will receive intravenous infusions of EMB-01 weekly (QW). The duration of each treatment cycle is 28 days (4 weeks). Dose escalation will continue until the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) is reached or all planned doses are administered. In part 2, participants will receive intravenous infusion of EMB-01 at the recommended Phase II dose (RP2D) regimen(s) once weekly. The duration of each treatment cycle is 28 days (4 weeks).

Who Is Running the Clinical Trial?

Shanghai EpimAb Biotherapeutics Co., Ltd.

Lead Sponsor

Trials

6

Recruited

600+

Covance

Industry Sponsor

Trials

124

Recruited

13,300+

Dr. Paul Kirchgraber

Covance

Chief Executive Officer since 2019

MD

Dr. Robert Dow

Covance

Chief Medical Officer since 2020

MD

Published Research Related to This Trial

The combination of nab-paclitaxel and carboplatin showed a 50% objective response rate in a small group of 10 elderly patients with advanced non-small cell lung cancer, but the study was halted early due to safety concerns, including two treatment-related deaths.

The treatment was associated with significant adverse effects, including severe neutropenia and infections, indicating that this chemotherapy regimen may be too toxic for elderly patients, highlighting the need for caution in treating this vulnerable population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of nanoparticle albumin-bound paclitaxel plus carboplatin as the first-line therapy in elderly patients with previously untreated advanced non-small cell lung cancer. Okuma, Y., Hosomi, Y., Takahashi, S., et al.[2022]

The epithelial-mesenchymal transition (EMT) is a key process that drives tumor malignancy and is linked to the development of cancer stem cells (CSCs), which are crucial for tumor initiation and progression.

Understanding the different variants of the EMT program and their molecular mechanisms is essential for developing targeted therapies against tumors, as these programs contribute to the plasticity and aggressiveness of cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epithelial-Mesenchymal Plasticity: A Central Regulator of Cancer Progression. Ye, X., Weinberg, RA.[2022]

Epithelial-mesenchymal transition (EMT) not only aids in cancer metastasis but also enhances cancer cell survival by activating stem cell programs and evading apoptosis, which may contribute to immune evasion in tumors.

Recent studies suggest that targeting EMT could lead to innovative therapies that reinvigorate the tumor microenvironment, making it more conducive to immune responses against tumors, with several promising approaches currently in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMT-induced immune evasion: connecting the dots from mechanisms to therapy. Imodoye, SO., Adedokun, KA.[2023]

Epithelial-mesenchymal transition (EMT) is a critical process that allows cancer cells to become more aggressive, enhancing their ability to initiate tumors, spread to other parts of the body, and resist treatments.

EMT not only alters the characteristics of cancer cells but also creates intermediate cell states that may act as cancer stem cells, influenced by signals from the tumor microenvironment, which can affect how the immune system responds to tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Dongre, A., Weinberg, RA.[2022]

Patients with advanced non-small-cell lung cancer (NSCLC) who responded to treatment with nab-paclitaxel/carboplatin within 6 weeks had significantly better overall survival (14.5 months) and progression-free survival (5.5 months) compared to nonresponders (10.3 months and 4.5 months, respectively).

Both early responders (within 6 weeks) and late responders (6-12 weeks) showed improved quality-adjusted time without symptoms or toxicity (Q-TWiST), indicating that response to treatment is a key indicator of long-term outcomes in NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality-adjusted Outcomes Stratified by Response in Patients With Advanced Non-Small-cell Lung Cancer Receiving First-line nab-Paclitaxel/Carboplatin or Paclitaxel/Carboplatin. Hirsh, V., Wan, Y., Lin, FJ., et al.[2019]

A phase I/II trial involving 46 patients with untreated advanced non-small cell lung cancer (NSCLC) demonstrated that the combination of carboplatin, nab-paclitaxel, and pembrolizumab is a safe and effective treatment, achieving a median overall survival of 15.4 months.

The study found a 35% overall response rate and a median progression-free survival of 5.6 months, indicating that this regimen can provide a durable benefit for patients, regardless of their PD-L1 status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Trial of Carboplatin, Nab-paclitaxel, and Pembrolizumab for Advanced Non-Small Cell Lung Cancer: Hoosier Cancer Research Network LUN13-175. Gentzler, RD., Mohindra, NA., Jalal, SI., et al.[2023]

Chemotherapy has been shown to improve survival and quality of life in patients with advanced non-small cell lung cancer, including those with poor performance status (PS2), who historically have been underrepresented in clinical trials.

Recent studies indicate that PS2 patients can benefit from chemotherapy, with combination treatments like carboplatin and paclitaxel potentially offering better outcomes than single-agent therapies, without significantly increased toxicity compared to fitter patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of chemotherapy in patients with poor performance status and advanced non-small cell lung cancer. Langer, C., Lilenbaum, R.[2019]

The modified carboplatin/nab-paclitaxel (CBDCA/nab-PTX) regimen showed a 6-month progression-free survival (PFS) rate of 20.8% in 17 untreated PS 2 patients with advanced non-small cell lung cancer, indicating some potential efficacy despite early study termination.

The study highlighted that patients whose performance status was not primarily due to disease burden had better overall survival rates, suggesting that factors like comorbidities may influence treatment outcomes and warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter, single-arm phase II study of modified carboplatin/nab-paclitaxel in untreated performance status 2 patients with advanced non-small cell lung cancer: TORG1426. Ichikawa, Y., Seki, N., Honda, T., et al.[2023]

Epithelial-mesenchymal transition (EMT) plays a crucial role in cancer metastasis by enabling cancer cells to become more invasive and potentially generating cancer stem cells, which can lead to therapy resistance.

Targeting the EMT pathway presents a promising strategy for developing therapies aimed at preventing metastasis in high-risk patients or eliminating existing metastatic cancer cells in those with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting EMT in cancer: opportunities for pharmacological intervention. Davis, FM., Stewart, TA., Thompson, EW., et al.[2022]

Targeting the epithelial-to-mesenchymal transition (EMT) is a promising strategy to combat tumor growth and spread, as well as to overcome resistance to chemotherapy and radiotherapy in various cancers.

An immunotherapeutic approach focusing on the T-box transcription factor T (brachyury), a key driver of EMT, is currently being evaluated in a Phase I clinical trial involving patients with advanced carcinomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An immunotherapeutic intervention against tumor progression: Targeting a driver of the epithelial-to-mesenchymal transition. Palena, C., Fernando, RI., Hamilton, DH.[2022]

Citations

1. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT168/761483/Abstract-CT168-EMB-01-an-EGFR-cMET-bispecific

Abstract CT168: EMB-01, an EGFR/cMET bispecific antibody ... Of the 29 pts, 7 (24.1%) achieved partial response (PR), and the disease control rate (DCR) was 86.2%. The median duration of response for 6 ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)00147-8/fulltext

22P EMB-01: An EGFR-cMET bispecific antibody, in ... The EMB-01 has a manageable safety profile consistent with EGFR and cMET inhibition. Preliminary anti-tumor evidence suggests EMB-01 can have activity in EGFR ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03797391

NCT03797391 | A Dose Escalation With Expansion Study ... This is a first-in-human (FIH), open-label, Phase I/II study of EMB-01, a bispecific Epidermal growth factor receptor (EGFR) and c-Mesenchymal-Epithelial ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(22)00147-8/pdf

22P EMB-01 Conclusions: Combination of sintilimab and anlotinib demonstrated durable efficacy and good tolerability in NSCLC patients with uncommon EGFR mutations. And ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05498389

NCT05498389 | EMB-01 in Combination With Osimertinib ... EMB-01 in combination with osimertinib may work better in treating patients with EGFR-mutant advanced non-small cell lung cancer. SECONDARY OBJECTIVES: I.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05176665

Study Details | NCT05176665 | EMB-01 in Patients With ... This study is to evaluate the safety and antitumor activity of EMB-01 in advanced/metastatic gastrointestinal cancers, including gastric cancer, hepatocellular ...

7. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03797391/

Clinical Trial: NCT03797391 This is a first-in-human (FIH), open-label, Phase I/II study of EMB-01, a bispecific Epidermal growth factor receptor (EGFR) and c-Mesenchymal-Epithelial ...

8. dana-farber.org dana-farber.org/clinical-trials/20-510

First-in-human, Phase I/II, Multicenter, Open-Label Study of ... First-in-human, Phase I/II, Multicenter, Open-Label Study of EMB-01 in Patients with Advanced/Metastatic Solid Tumors.