BLYG8824A for Colorectal Cancer

No longer recruiting at 12 trial locations

Overseen By Reference Study ID Number: GO41751 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Genentech, Inc.

Must not be taking: QT-prolonging medications

Disqualifiers: Pregnancy, Cardiopulmonary dysfunction, Liver disease, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment, BLYG8824A, for individuals with colorectal cancer that has spread or cannot be surgically removed. The main goal is to assess the safety, tolerability, and behavior of this treatment in the body, while also evaluating its potential to shrink tumors. The trial consists of two parts: one to determine the optimal dose and another to test that dose more broadly. Individuals who have tried other standard treatments for advanced colorectal cancer without success or tolerance may be suitable candidates for this study. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those on medications that prolong the QT interval (a heart rhythm measure). It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that BLYG8824A is likely to be safe for humans?

Research shows that BLYG8824A is in the early stages of testing to determine its safety and tolerability in humans. Researchers are beginning to understand its safety profile. In these initial studies, participants receive gradually increasing doses to identify the highest dose that can be taken without serious side effects. This process helps pinpoint any side effects and their severity.

Since BLYG8824A is in a Phase 1 trial, the primary focus is on safety rather than efficacy. This phase is crucial to ensure the treatment is not harmful before assessing its effectiveness in later stages. Although detailed information on side effects from these early studies is not yet available, the trial closely monitors participants for any adverse reactions.

Overall, BLYG8824A is still undergoing thorough testing to ensure its safety for future use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for colorectal cancer, which typically include chemotherapy, radiation, and targeted therapies, BLYG8824A is unique because it may offer a novel approach by targeting pathways not addressed by existing options. Researchers are excited about BLYG8824A because it potentially works through a new mechanism of action that could enhance effectiveness or reduce side effects. This innovative approach could lead to improved outcomes for patients who have not responded well to traditional treatments.

What evidence suggests that BLYG8824A might be an effective treatment for colorectal cancer?

Research shows that BLYG8824A is a new drug under investigation for its potential to fight colorectal cancer. Early studies suggest it might shrink or slow cancer growth. In this trial, participants will join different treatment arms to assess the drug's safety and tolerability at various doses. While clinical data remains limited, the drug's mechanism appears promising for treating advanced colorectal cancer. ^{2 4 5 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Genentech, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic colorectal cancer that's worsened after standard treatments. Participants should be in fairly good physical shape (ECOG 0-1), have measurable disease, and their body functions must meet certain standards. They can't join if they have significant liver disease, active hepatitis B or C, HIV, uncontrolled diabetes, autoimmune diseases, are pregnant/breastfeeding or planning to become pregnant soon.

Inclusion Criteria

I can provide a tissue sample for the study, either from previous or new biopsies.

My condition worsened or I couldn't tolerate treatments including oxaliplatin and anti-EGFR.

Any severe side effects from my previous treatments have mostly gone away.

Exclusion Criteria

I am taking medication that can affect my heart's rhythm.

My cancer has spread to the lining of my brain and spinal cord.

My spinal cord compression hasn't been treated with surgery or radiation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-Escalation Stage

Participants will be assigned sequentially to escalating doses of BLYG8824A, up to the maximum tolerated dose (MTD)

Duration not specified

Dose-Expansion Stage

Once dose escalation is completed and the MTD (or MAD) has been identified, a recommended expansion dose will be proposed for the dose-expansion stage of the trial

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 months

What Are the Treatments Tested in This Trial?

Interventions

• BLYG8824A

Trial Overview The study tests BLYG8824A's safety and how the body processes it. It also looks at its initial effectiveness against colorectal cancer that has spread or cannot be removed by surgery. The trial includes patients who've had previous treatments and requires tissue samples for enrollment.

How Is the Trial Designed?

Group I: Dose-Expansion Stage Experimental Treatment 1 Intervention

Once dose escalation is completed and the MTD (or MAD) has been identified, a recommended expansion dose will be proposed for the dose-expansion stage of the trial.

Group II: Dose-Escalation Stage Experimental Treatment 1 Intervention

Participants will be assigned sequentially to escalating doses of BLYG8824A, up to the maximum tolerated dose (MTD).

Who Is Running the Clinical Trial?

Genentech, Inc.

Lead Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

In a study of 319 patients with colorectal cancer and metastatic liver lesions, combined treatments including surgery, radiofrequency ablation (RFA), and microwave ablation (MWA) significantly improved survival rates, with 5-year survival after liver resection at 24.6%.

Minimally invasive techniques like RFA and MWA not only increased the resectability of tumors to 35-40% but also reduced surgical risks for critically ill patients, demonstrating their efficacy in managing liver metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combined treatment of colorectal cancer followed by metastatic liver injury]. Prazdnikov, EN., Sizova, AN., Svetashov, VS., et al.[2019]

PD-1/PD-L1 inhibitors show a promising objective response rate of 33% in treating colorectal cancer (CRC), particularly effective in patients with deficient mismatch repair, achieving a response rate of 43%.

The treatment is associated with an overall survival rate of 56% and a progression-free survival rate of 46%, indicating its efficacy, while the adverse event rate is manageable at 59%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of PD-1/PD-L1 and CTLA-4 immune checkpoint inhibitors in colorectal cancer: a meta-analysis. Jin, C., Zhu, X., Huang, X., et al.[2022]

M7824, a novel bifunctional fusion protein targeting PD-L1 and TGFβ, demonstrated a manageable safety profile in a phase I trial with 19 heavily pretreated patients, with no maximum tolerated dose reached.

Early efficacy signals were observed, including one complete response in cervical cancer and two partial responses in pancreatic and anal cancers, suggesting potential for further investigation in various tumor types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, in Advanced Solid Tumors. Strauss, J., Heery, CR., Schlom, J., et al.[2022]

Pembrolizumab significantly improved progression-free survival (PFS) in patients with unresectable or metastatic microsatellite instability-high (MSI-H) colorectal cancer, with a median PFS of 16.5 months compared to 8.2 months for standard chemotherapy, indicating its efficacy as a first-line treatment.

The FDA found no safety concerns during the approval process, and while both pembrolizumab and standard of care had similar adverse reactions, the duration of treatment with pembrolizumab was nearly double that of standard care, suggesting a potentially more favorable treatment profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the First-line Treatment of Patients with MSI-H/dMMR Advanced Unresectable or Metastatic Colorectal Carcinoma. Casak, SJ., Marcus, L., Fashoyin-Aje, L., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04468607

NCT04468607 | A Study of BLYG8824A in Participants ... This study will evaluate the safety, tolerability, and pharmacokinetics of BLYG8824A and will make a preliminary assessment of the anti-tumor activity of ...

2. withpower.com withpower.com/trial/phase-1-colorectal-neoplasms-7-2020-bd095

BLYG8824A for Colorectal Cancer · Info for Participants This trial is testing a new drug called BLYG8824A to see if it is safe and effective in patients with advanced colorectal cancer.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11395697/

From Crypts to Cancer: A Holistic Perspective on ... This article provides a comprehensive review of our current understanding of CRC epidemiology, risk factors, molecular pathogenesis, and management strategies.

4. forpatients.roche.com forpatients.roche.com/en/trials/cancer/crc/a-study-of-blyg8824a-in-participants-with-locally-advan-69775.html

Clinical Trial – Colorectal Cancer – Safety and Pharmacok... Access the dose escalation study of BLYG8824A to know its safety, tolerability, and pharmacokinetics as an anti-tumor agent in patients with locally ...

5. australianclinicaltrials.gov.au australianclinicaltrials.gov.au/anzctr-search-results?search_text=&condition_category=all&condition_code=all&recruitment_status=all&ethics_approval=all&page=2376

ANZCTR search results | Australian Clinical ... This study will evaluate the safety, tolerability, and pharmacokinetics of BLYG8824A and will make a preliminary assessment of the anti-tumor activity of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04468607

NCT04468607 | A Study of BLYG8824A in Participants ... This study will evaluate the safety, tolerability, and pharmacokinetics of BLYG8824A and will make a preliminary assessment of the anti-tumor activity of BLYG ...

7. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT157/761843/Abstract-CT157-Phase-1-dose-escalation-study-of

Phase 1 dose-escalation study of linclatamig, a LY6G6D×CD3 ... This study evaluated the safety, pharmacokinetics (PK), biomarkers, and anti-tumor activity of linclatamig in patients (pts) with LY6G6D+ mCRC.