Combo Therapy for Colorectal Cancer

Not currently recruiting at 112 trial locations

Overseen By BeiGene

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BeiGene

Must not be taking: Anti-EGFR, T-cell checkpoint

Disqualifiers: BRAF V600E, MSI-H, dMMR, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs to evaluate their effectiveness in treating colorectal cancer. It compares various drug combinations, including LBL-007 (an anti-LAG-3 monoclonal antibody) and tislelizumab, both alone and with standard treatments like bevacizumab (Avastin) and fluoropyrimidine. The goal is to determine which combination is most effective and safe for patients. Individuals with colorectal cancer that cannot be surgically removed and who have not received advanced-stage treatments may be suitable candidates. As a Phase 1 and Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking cancer treatment advancements.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, since the trial involves specific cancer treatments, it's best to discuss your current medications with the trial team.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it does mention that participants should not have had certain prior therapies, 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 LBL-007, a type of antibody, is generally safe for humans. When combined with other treatments, it maintains a manageable safety profile, with most side effects being non-serious. Recent trials have not identified any new safety concerns.

Tislelizumab, another drug in this trial, has undergone testing in many cancer patients. It also exhibits a manageable safety profile, with side effects that can be handled. Data from over 1,950 patients indicate it is safe when used with chemotherapy.

Bevacizumab and fluoropyrimidine (such as capecitabine or 5-FU) have received approval for treating various cancers. They are generally safe for most people, although side effects can occur.

This trial is in the early stages, so researchers continue to learn about the safety of these drug combinations. Early trials focus on safety, and participation helps confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for colorectal cancer because they combine innovative immunotherapy agents with existing drugs, potentially enhancing effectiveness. LBL-007 is an exciting addition, as it may help modulate immune responses more effectively when paired with Tislelizumab, another immunotherapy that blocks PD-1, a protein that prevents the immune system from attacking cancer cells. This combo is further bolstered with Bevacizumab, which inhibits blood vessel growth in tumors, and either Capecitabine or 5-FU, both of which interfere with DNA synthesis in cancer cells. Together, these combinations aim to attack the cancer through multiple pathways, offering hope for more comprehensive and effective treatments compared to standard therapies like chemotherapy alone.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

Research has shown that LBL-007, a new treatment, can slow tumor growth and help destroy cancer cells when combined with anti-PD-1 treatments. This trial includes various combinations of LBL-007, Tislelizumab, Bevacizumab, and either Capecitabine or 5-FU. Tislelizumab, a key component of the treatment, has demonstrated lasting effects against tumors in patients who have undergone extensive treatment for colorectal cancer, although some studies suggest it may not be as effective in certain situations. Bevacizumab, part of this treatment mix, is already known to manage colorectal cancer by cutting off the blood supply to tumors. Capecitabine and 5-FU, traditional chemotherapy drugs, work by stopping cancer cells from growing. Together, these treatments aim to fight colorectal cancer more effectively than standard treatments alone. ^{6 7 8 9 10}

Who Is on the Research Team?

Study Director

Principal Investigator

BeiGene

Are You a Good Fit for This Trial?

This trial is for adults with colorectal cancer that's spread or can't be surgically removed. They should have had some initial treatment and their disease must not have worsened. No prior treatments in the metastatic setting are allowed, except first-line therapy, and they shouldn't have certain genetic mutations or immune system conditions.

Inclusion Criteria

Participant must have measurable disease as defined per RECIST version 1.1

My cancer has not worsened after initial treatment.

My colorectal cancer is at stage IV and cannot be surgically removed.

Exclusion Criteria

I have been treated with an anti-EGFR antibody.

I have received treatments that boost or target my immune system.

My cancer cannot be surgically removed after initial treatment, according to my doctor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LBL-007 plus tislelizumab in combination with bevacizumab plus fluoropyrimidine or bevacizumab plus fluoropyrimidine alone

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Capecitabine
• LBL-007
• Tislelizumab

Trial Overview The study tests LBL-007 plus Tislelizumab combined with Bevacizumab and a fluoropyrimidine (like 5-Fluorouracil or Capecitabine) against just Bevacizumab with a fluoropyrimidine. It aims to see if adding LBL-007 and Tislelizumab improves treatment outcomes.

How Is the Trial Designed?

Group I: Phase 2: Arm B: LBL-007 + Bevacizumab + Fluoropyrimidine Experimental Treatment 4 Interventions

LBL-007 (high dose) + bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)

Group II: Phase 2: Arm A and Arm D: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine Experimental Treatment 5 Interventions

LBL-007 (high dose) + tislelizumab (low dose every 3 weeks or high dose every 4 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)

Group III: Phase 1b: Cohort 2: LBL-007 + Tislelizumab + Bevacizumab + Fluoropyrimidine Experimental Treatment 5 Interventions

LBL-007 (high dose) + tislelizumab (low dose every 3 weeks or high dose every 4 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)

Group IV: Phase 1b: Cohort 1b: LBL-007 + Tislelizumab + Bevacizumab + 5-Fluorouracil (5-FU) Experimental Treatment 4 Interventions

LBL-007 (medium dose) + tislelizumab (high dose once every 4 weeks) + bevacizumab (5 mg/kg once every 2 weeks) + 5-FU

Group V: Phase 1b: Cohort 1a: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine Experimental Treatment 4 Interventions

LBL-007 (medium dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine

Group VI: Phase 1b: Cohort -1: LBL-007 + Tislelizumab + Bevacizumab + Capecitabine Experimental Treatment 4 Interventions

LBL-007 (low dose) + tislelizumab (low dose once every 3 weeks) + bevacizumab (7.5 mg/kg once every 3 weeks) + capecitabine

Group VII: Phase 2: Arm C and Arm E: Bevacizumab + Fluoropyrimidine Active Control 5 Interventions

Bevacizumab (7.5 mg/kg once every 3 weeks or 5 mg/kg once every 2 weeks) + fluoropyrimidine (5-FU or capecitabine)

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

In a phase II trial involving 209 patients with metastatic colorectal cancer, the addition of bevacizumab to fluorouracil and leucovorin (FU/LV) significantly improved median progression-free survival to 9.2 months compared to 5.5 months with placebo, indicating a strong therapeutic benefit.

While bevacizumab treatment was associated with a higher incidence of grade 3 hypertension (16% vs. 3% in the placebo group), this side effect was manageable with medication and did not lead to discontinuation of the treatment, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. Kabbinavar, FF., Schulz, J., McCleod, M., et al.[2022]

In a combined analysis of three studies involving 490 patients, the addition of bevacizumab to FU/LV treatment resulted in a median overall survival of 17.9 months, compared to 14.6 months for the control group, indicating a significant survival benefit.

Patients receiving FU/LV with bevacizumab also experienced improved progression-free survival (8.8 months vs. 5.6 months) and a higher response rate (34.1% vs. 24.5%), demonstrating the efficacy of bevacizumab in treating metastatic colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. Kabbinavar, FF., Hambleton, J., Mass, RD., et al.[2022]

Bevacizumab, a targeted therapy that inhibits vascular endothelial growth factor, significantly improves treatment outcomes in metastatic colorectal cancer when added to standard chemotherapy, showing a higher objective response rate (40% vs. 17%) and longer median survival (21.5 months vs. 13.8 months).

While bevacizumab is associated with manageable safety concerns such as hypertension and thrombosis, its efficacy in extending time to disease progression (9.0 months vs. 5.2 months) highlights its potential as a valuable addition to colorectal cancer treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapy of colorectal cancer: clinical experience with bevacizumab. Fernando, NH., Hurwitz, HI.[2019]

In a study of 813 patients with untreated metastatic colorectal cancer, adding bevacizumab to standard chemotherapy significantly improved median survival, regardless of the levels of VEGF, THBS-2, or microvessel density.

The analyses indicated that while high THBS-2 expression might suggest a potential survival benefit from bevacizumab, it was not statistically significant, reinforcing that bevacizumab's effectiveness is independent of these specific biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of vascular endothelial growth factor-A expression, thrombospondin-2 expression, and microvessel density on the treatment effect of bevacizumab in metastatic colorectal cancer. Jubb, AM., Hurwitz, HI., Bai, W., et al.[2022]

In a phase 2 clinical trial involving 133 patients with refractory metastatic colorectal cancer, the addition of atezolizumab to capecitabine and bevacizumab therapy resulted in a median progression-free survival (PFS) of 4.4 months compared to 3.6 months for the placebo group, indicating a potential benefit, although not clinically meaningful.

Patients with microsatellite-stable disease and those without liver metastasis showed greater benefits from the combination therapy, suggesting that specific patient characteristics may influence the efficacy of atezolizumab in this treatment context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Capecitabine and Bevacizumab With or Without Atezolizumab for the Treatment of Refractory Metastatic Colorectal Cancer: A Randomized Clinical Trial. Mettu, NB., Ou, FS., Zemla, TJ., et al.[2022]

This study aims to evaluate the efficacy and safety of ramucirumab, a monoclonal antibody targeting VEGFR-2, in treating advanced colorectal cancer through a systematic review of randomized controlled trials.

The review will assess various clinical outcomes, including overall survival and adverse events, using data from multiple databases and will provide evidence-based guidance for clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ramucirumab treatment in patients with advanced colorectal cancer: A protocol for systematic review and meta analysis. Ju, M., Cheng, H., Qu, K., et al.[2023]

In a randomized phase II study involving 83 patients with irinotecan-refractory metastatic colorectal cancer, the combination of cetuximab and bevacizumab with irinotecan (CBI) showed a longer time to tumor progression (7.3 months) and a higher response rate (37%) compared to cetuximab and bevacizumab alone (CB), which had a time to progression of 4.9 months and a response rate of 20%.

The concurrent administration of cetuximab and bevacizumab was found to be safe, with toxicity profiles similar to those expected from the individual agents, suggesting that this combination therapy is a feasible option for patients who have not previously been treated with these drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II trial of cetuximab, bevacizumab, and irinotecan compared with cetuximab and bevacizumab alone in irinotecan-refractory colorectal cancer: the BOND-2 study. Saltz, LB., Lenz, HJ., Kindler, HL., et al.[2022]

Metastatic colorectal cancer (CRC) patients showed significantly lower immune responses at baseline compared to healthy donors, but these responses improved during treatment with either irinotecan/5-fluorouracil/leucovorin (IFL) or IFL combined with bevacizumab (B-IFL).

The combination of IFL with bevacizumab (B-IFL) resulted in greater increases in key immune markers (like IL-2 and IFN-γ) compared to IFL alone, suggesting that B-IFL may enhance immune function in CRC patients during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined treatment with bevacizumab and standard chemotherapy restores abnormal immune parameters in advanced colorectal cancer patients. Tsavaris, N., Voutsas, IF., Kosmas, C., et al.[2021]

Bevacizumab, an anti-angiogenic monoclonal antibody, has been shown to extend survival in patients with metastatic colorectal cancer when used alongside chemotherapy.

Recent studies suggest that combining bevacizumab with oxaliplatin-containing chemotherapy regimens may further enhance patient outcomes, indicating a potential strategy for improving treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab plus oxaliplatin-based regimens for the treatment of colorectal cancer. Scheithauer, W., Schmiegel, W.[2018]

In a study involving 34 heavily pre-treated patients with metastatic colorectal cancer, the combination of capecitabine and bevacizumab was found to be safe and well tolerated, showing an acceptable toxicity profile.

The treatment resulted in a median progression-free survival of 5.4 months and a median overall survival of 12.2 months, indicating significant disease control in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capecitabine and bevacizumab in heavily pre-treated patients with advanced colorectal cancer. Larsen, FO., Boisen, MK., Fromm, AL., et al.[2015]

Adjuvant therapy using monoclonal antibodies like Bevacizumab, Cetuximab, and Panitumumab can significantly reduce the risk of disease recurrence in patients with stage II-IV colorectal cancer, improving clinical outcomes.

Bevacizumab works by targeting and reversing proangiogenic molecules, while Cetuximab and Panitumumab target the epidermal growth factor receptor, and their combination with chemotherapy has shown to be more effective than using either treatment alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted therapy in colorectal cancer. Wadler, S.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12559405/

Novel anti-LAG-3 antibody LBL-007 with anti-PD-1 blockade ... The combination of LBL-007 and anti-PD-1 antibodies delayed tumor growth and promoted tumor cell apoptosis compared with monotherapy in human ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9832734/

A first-in-human study of the anti-LAG-3 antibody ... Here, we evaluate the antitumor activity of the LAG-3 antibody favezelimab alone or in combination with pembrolizumab in participants with MSS mCRC.

3. nature.com nature.com/articles/s44276-024-00118-x

CITRINO: phase 1 dose escalation study of anti-LAG-3 ... Dual programmed cell death protein (ligand)-1 (PD-[L]1) and lymphocyte-activation gene-3 (LAG-3) blockade has demonstrated improved anti-tumour ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05609370?id=BGB-A317-LBL-007-201&rank=1

A Study Investigating the Efficacy and Safety of LBL-007 ... This is a Phase 1b/2 study to investigate the efficacy and safety of LBL-007 plus tislelizumab when administered in combination with bevacizumab plus ...

5. tandfonline.com tandfonline.com/doi/full/10.1080/19420862.2019.1629239

Characterization of a novel anti-human lymphocyte ... In conclusion, we identified and characterized a fully human anti-LAG-3 antibody, LBL-007. LBL-007 could suppress the growth of mouse colorectal ...

6. nature.com nature.com/articles/s41598-025-21400-z

Novel anti-LAG-3 antibody LBL-007 with anti-PD-1 ... The combination of LBL-007 and anti-PD-1 antibodies delayed tumor growth and promoted tumor cell apoptosis compared with monotherapy in human ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.9541

Updated safety and efficacy results from the phase I study ... Conclusions: LBL-007 plus toripalimab continued to show promising antitumor activity and manageable safety profile in patients with treatment- ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11806529/

Anti-LAG-3 antibody LBL-007 plus anti-PD-1 ... In this trial, we evaluate the safety profile, preliminary antitumor activity, and potential biomarkers of LBL-007 combined with toripalimab in ...

9. asco.org asco.org/abstracts-presentations/ABSTRACT330291

Phase I study of LBL-007, a novel anti-human lymphocyte ... It has shown that LBL-007 significantly inhibited tumor growth in a mouse MC38 tumor model in hLAG-3 knock-in mice with more pronounced tumor inhibition when ...

10. beonemedinfo.com beonemedinfo.com/CongressDocuments/Lenz_Liberty-201_AACR_Poster_2024.pdf

Liberty-201 is an ongoing phase 1b/2 trial investigating the ... • Emerging safety data of LBL-007 in combination with an anti–PD-1 antibody demonstrated a well-tolerated profile with no new safety signals ...