Combo Therapy for Colorectal Cancer

Recruiting at 110 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

113 Participants Needed

Trial Summary

What is the purpose of this trial?

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 fluoropyrimidine, and LBL-007 in combination with bevacizumab plus fluoropyrimidine versus bevacizumab plus fluoropyrimidine to participants with colorectal cancer.

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.

What data supports the idea that Combo Therapy for Colorectal Cancer is an effective treatment?

The available research shows that combining bevacizumab with chemotherapy improves outcomes for patients with metastatic colorectal cancer. Studies indicate that this combination can increase survival rates and improve clinical outcomes compared to chemotherapy alone. For example, adding bevacizumab to standard chemotherapy regimens like irinotecan, fluorouracil, and leucovorin has been shown to significantly prolong survival. Additionally, using bevacizumab with oxaliplatin-based chemotherapy regimens is also promising for improving patient outcomes. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination therapy for colorectal cancer?

Research shows that adding bevacizumab, a drug that targets blood vessel growth, to standard chemotherapy can improve survival in patients with advanced colorectal cancer. Studies have demonstrated that this combination therapy can restore immune function and prolong survival compared to chemotherapy alone. ^{1 2 3 4 5}

What safety data is available for the combo therapy in colorectal cancer?

Safety data for the combo therapy involving Bevacizumab (Avastin) and Capecitabine (Xeloda) in colorectal cancer is available from several studies. The BOND-2 study evaluated the safety of Bevacizumab combined with Cetuximab in metastatic colorectal cancer. Another study assessed the safety of Capecitabine and Bevacizumab in heavily pre-treated patients with advanced colorectal cancer. These studies provide insights into the safety profile of these drugs when used in combination for colorectal cancer treatment. ^{3 6 7 8 9}

What safety data exists for the combination therapy involving Bevacizumab and Capecitabine in colorectal cancer?

Studies have evaluated the safety of Bevacizumab and Capecitabine in patients with advanced colorectal cancer, showing that these drugs have been used safely in heavily pre-treated patients. Bevacizumab, in particular, has been studied in combination with other treatments and is generally considered safe, although specific side effects can vary. ^{3 6 7 8 9}

Is the drug combination of Bevacizumab, Capecitabine, LBL-007, and Tislelizumab promising for colorectal cancer?

Yes, the drug combination is promising for colorectal cancer. Bevacizumab, when combined with chemotherapy, has shown to improve survival rates and restore immune function in patients with advanced colorectal cancer. It targets the growth of new blood vessels that tumors need to grow, making it an effective part of cancer treatment. ^{1 3 7 10 11}

What makes the Combo Therapy for Colorectal Cancer unique?

This combo therapy is unique because it combines Bevacizumab, Capecitabine, LBL-007, and Tislelizumab, targeting both the blood vessels that feed tumors and the immune system to fight cancer cells. This approach is different from standard treatments that typically focus on chemotherapy alone. ^{1 3 7 10 11}

Research Team

Study Director

Principal Investigator

BeiGene

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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 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]

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]

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]

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]

References

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

Combined treatment with bevacizumab and standard chemotherapy restores abnormal immune parameters in advanced colorectal cancer patients. [2021]

2. United States 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. [2022]

3. United States 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. [2022]

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

Targeted therapy in colorectal cancer. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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

6. United States 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. [2023]

7. United States 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. [2022]

8. United States 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Capecitabine and bevacizumab in heavily pre-treated patients with advanced colorectal cancer. [2015]

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

Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Targeted therapy of colorectal cancer: clinical experience with bevacizumab. [2019]