BLYG8824A for Colorectal Cancer

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

46 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called BLYG8824A to see if it is safe and effective in patients with advanced colorectal cancer. The goal is to find out if the drug can shrink tumors or stop them from growing.

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.

What data supports the effectiveness of the drug BLYG8824A for colorectal cancer?

The research on targeting the epidermal growth factor receptor (EGFR) in colorectal cancer shows that drugs inhibiting EGFR have shown preliminary evidence of antitumor efficacy. This suggests that treatments like BLYG8824A, if they target similar pathways, might also be effective. ^{1 2 3 4 5}

Is BLYG8824A safe for humans?

The treatment M7824, which targets PD-L1 and TGF-β, has been tested in patients with advanced solid tumors and showed a manageable safety profile, with some patients experiencing serious side effects like skin infection and colitis. In colorectal cancer, similar treatments targeting PD-L1 have shown acceptable safety with common side effects including diarrhea and fatigue. ^{6 7 8 9 10}

Research Team

Clinical Trials

Principal Investigator

Genentech, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Combined treatment of colorectal cancer followed by metastatic liver injury]. [2019]

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

Combined modality therapy including intraoperative electron irradiation for locally recurrent colorectal cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

A randomised, double-blind, placebo-controlled phase 2 study of trebananib (AMG 386) in combination with FOLFIRI in patients with previously treated metastatic colorectal carcinoma. [2021]

4. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[The possibilities to improve the outcomes in patients with colon cancer complicated by acute obstruction]. [2019]

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

Epidermal growth factor receptor as a therapeutic target for the treatment of colorectal cancer. [2019]

6. England 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. [2022]

7. United States 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. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Dual targeting of TGF-β and PD-L1 inhibits tumor growth in TGF-β/PD-L1-driven colorectal carcinoma. [2023]

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

Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, in Advanced Solid Tumors. [2022]

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

Genomically informed small-molecule drugs overcome resistance to a sustained-release formulation of an engineered death receptor agonist in patient-derived tumor models. [2021]