Atezolizumab + Bevacizumab for Gastrointestinal Cancer

(MRD-GI Trial)

Recruiting at 2 trial locations

Overseen By Loyanna Hubbard

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Georgetown University

Must not be taking: NSAIDs, Immunosuppressants, Anticoagulants, others

Disqualifiers: Autoimmune disease, Cardiovascular disease, Active infection, others

Stay on Your Current Meds You can continue your current medications while participating

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 6

Duration: 12 months

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a non-randomized, open-label, multi-cohort, multi-site, pilot feasibility therapeutic trial. The study will enroll 20 patients across 4 cohorts (CRC, gastric, PDAC, and HCC/intra-hepatic-/extra-hepatic-, gall bladder adenocarcinomas) diagnosed with histologically confirmed GI cancers. These patients will have already completed all Standard of Care (SOC) treatments (including neoadjuvant, surgery, local therapies, and/or adjuvant therapy as applicable), as defined by the treating primary physician or research team, with curative intent but have a positive SignateraTM tumor-informed ctDNA test and NED radiographically by standard imaging within 28 days prior to enrollment and within 1 year of completing all curative-intent therapy. All patients will be treated with intravenous (IV) atezolizumab 1200 mg IV and bevacizumab 15 mg/kg on Day 1 of 21-day cycles until disease recurrence, ctDNA POD, unacceptable toxicity, or subject withdrawal of consent with a maximum 12 month total duration of study therapy. Atezolizumab and bevacizumab drug will be provided.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that certain medications, like high-dose aspirin, clopidogrel, and chronic NSAIDs, should not be used close to the start of the study treatment. It's best to discuss your current medications with the study team to get specific guidance.

What data supports the effectiveness of the drug combination Atezolizumab and Bevacizumab for gastrointestinal cancer?

Bevacizumab (Avastin) has shown significant benefits in improving survival and delaying disease progression when combined with chemotherapy in colorectal cancer, which is a type of gastrointestinal cancer. This suggests that Bevacizumab may also be effective in other gastrointestinal cancers when used in combination with other treatments like Atezolizumab. ^{1 2 3 4 5}

Is the combination of Atezolizumab and Bevacizumab generally safe for humans?

The combination of Atezolizumab (Tecentriq) and Bevacizumab (Avastin) has been studied for safety in various conditions, including liver cancer. Common side effects of Bevacizumab include high blood pressure, protein in urine, and bleeding, which are usually mild to moderate and manageable. Serious but less common side effects include issues with wound healing and gastrointestinal perforation. ^{6 7 8 9 10}

How is the drug combination of Atezolizumab and Bevacizumab unique for treating gastrointestinal cancer?

The combination of Atezolizumab and Bevacizumab is unique because it targets both the immune system and blood vessel growth in tumors. Atezolizumab helps the immune system recognize and attack cancer cells, while Bevacizumab blocks the growth of blood vessels that supply nutrients to tumors, potentially enhancing the overall anticancer effect. ^{3 4 11 12 13}

Research Team

John L. Marshall, MD

Principal Investigator

Georgetown University

Eligibility Criteria

Adults who've completed all standard treatments for certain GI cancers (like colorectal, stomach, liver cancer) with curative intent but still have detectable ctDNA. They must be in good physical condition, not pregnant or breastfeeding, willing to use contraception and not have any active infections or severe health conditions that could interfere with the trial.

Inclusion Criteria

Signed Informed Consent Form

Women of childbearing potential must have a negative serum test result within 28 days prior to initiation of study treatment

Agreement to refrain from donating sperm for men

Exclusion Criteria

I have high calcium levels in my blood that are causing symptoms.

I might have or know I have cancer that has come back or spread within the last 28 days.

I have a serious heart condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive intravenous atezolizumab and bevacizumab on Day 1 of 21-day cycles for a maximum of 12 months

12 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

2 visits (in-person)

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Atezolizumab
• Bevacizumab

Trial Overview The trial is testing Atezolizumab and Bevacizumab on patients with GI cancers who are ctDNA positive after standard treatment. It's an open-label study where everyone gets the drugs through IV every 21 days for up to a year unless their disease returns or side effects become too much.

Participant Groups

Group I: Atezolizumab plus Bevacizumab Experimental Treatment 2 Interventions

atezolizumab 1200 mg and bevacizumab 15 mg/kg given intravenously on Day 1 of each 21-day cycle (every 3 weeks \[Q3W\]) for a maximum of 12 months.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Georgetown University

Lead Sponsor

Trials

355

Recruited

142,000+

Genentech, Inc.

Industry 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

Natera, Inc.

Industry Sponsor

Trials

56

Recruited

50,700+

Findings from Research

Bevacizumab (Avastin) significantly improves overall and progression-free survival in patients with metastatic colorectal cancer when combined with standard chemotherapy regimens like IFL or 5-FU/LV, based on clinical data from various trials.

The drug shows potential for use in both first-line and second-line treatments, as well as in the adjuvant setting, by inhibiting vascular endothelial growth factor to prevent tumor angiogenesis, with ongoing Phase III trials exploring its efficacy in combination with oxaliplatin-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future development of bevacizumab in colorectal cancer. Díaz-Rubio, E., Schmoll, HJ.[2015]

Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, has shown significant antitumor activity, particularly in renal cell carcinoma, where it extended the time to tumor progression compared to placebo.

In advanced colorectal cancer, adding bevacizumab to chemotherapy resulted in significantly longer overall survival and progression-free survival, indicating its effectiveness when combined with standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanding the clinical development of bevacizumab. Chen, HX.[2019]

Bevacizumab (Avastin) is an FDA-approved treatment for metastatic colorectal cancer, specifically used in combination with 5-fluorouracil-based chemotherapy since February 2004.

As the first approved drug targeting tumor angiogenesis, bevacizumab works by inhibiting vascular endothelial growth factor (VEGF), which is crucial for tumor blood vessel formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab. Ellis, LM.[2020]

In a phase IV trial involving 209 treatment-naïve patients with metastatic colorectal cancer, the combination of bevacizumab and FOLFIRI resulted in a median progression-free survival (PFS) of 11.1 months and a median overall survival (OS) of 22.2 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with most adverse events being mild (grade 1/2), while serious side effects like neutropenia and venous thromboembolic events occurred in over 10% of patients, indicating manageable safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer. Sobrero, A., Ackland, S., Clarke, S., 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]

Bevacizumab (Avastin) effectively targets VEGF to inhibit tumor angiogenesis, showing a safety profile that includes mostly mild to moderate side effects such as hypertension and proteinuria, which are manageable in clinical settings.

The side effects associated with bevacizumab, including rare but serious events like gastrointestinal perforation and arterial thrombosis, do not typically exacerbate the toxicity of standard chemotherapy, making it a suitable adjunct treatment for metastatic colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing patients treated with bevacizumab combination therapy. Gordon, MS., Cunningham, D.[2015]

In a multicenter study of 121 patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Ate/Bev), the objective response rate was 24% and the disease control rate was 76%, demonstrating real-world efficacy similar to phase III trial results.

The most common severe side effect was an increase in aspartate aminotransferase levels (10.7%), and factors like elevated baseline neutrophil-to-lymphocyte ratio were linked to poorer progression-free and overall survival, indicating the need for careful monitoring in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma. Cheon, J., Yoo, C., Hong, JY., et al.[2022]

Bevacizumab, when combined with chemotherapy (like irinotecan/5-FU/leucovorin), significantly improves survival rates in patients with metastatic colorectal cancer, leading to its approval for first-line treatment.

While generally well-tolerated, bevacizumab can cause manageable side effects such as hypertension (3-16%) and other serious but less common toxicities, highlighting the need for guidelines on managing these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and management of bevacizumab-related toxicities in colorectal cancer. Saif, MW., Mehra, R.[2022]

In a phase 3 trial involving 501 patients with unresectable hepatocellular carcinoma, the combination of atezolizumab and bevacizumab significantly improved overall survival (67.2% at 12 months) and progression-free survival (6.8 months) compared to sorafenib.

The treatment with atezolizumab-bevacizumab showed a lower risk of death (hazard ratio 0.58) and similar rates of severe adverse events compared to sorafenib, indicating a favorable safety profile despite some instances of grade 3 or 4 hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. Finn, RS., Qin, S., Ikeda, M., et al.[2021]

In a study of 286 patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab, treatment-related hypertension was linked to better progression-free survival, with a median of 12.6 months compared to 6.5 months for those without hypertension.

Conversely, treatment-related fatigue was associated with shorter overall survival, indicating that while hypertension may signal a positive response to treatment, fatigue could indicate poorer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab. Tada, T., Kumada, T., Hiraoka, A., et al.[2023]

In a phase Ib study involving 20 patients with platinum-resistant ovarian cancer, the combination of atezolizumab and bevacizumab demonstrated a safety profile consistent with the individual drugs, with 95% experiencing treatment-related adverse events, but no grade 5 events reported.

The treatment resulted in a 15% overall response rate, with some patients achieving durable responses lasting up to 18.9 months, and a disease control rate of 55%, indicating potential efficacy in managing this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Clinical Activity of Atezolizumab Plus Bevacizumab in Patients with Ovarian Cancer: A Phase Ib Study. Moroney, JW., Powderly, J., Lieu, CH., et al.[2021]

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 (Avastin) is an effective anti-VEGF therapy that significantly improves progression-free survival in patients with metastatic colorectal cancer, making it a key treatment option approved by the FDA and European Medicines Agency.

Ongoing clinical studies are exploring the use of bevacizumab in other gastrointestinal cancers, and there is a need for continued development of new antiangiogenic therapies as tumors may develop resistance to current treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug insight: antiangiogenic therapies for gastrointestinal cancers--focus on monoclonal antibodies. Reinacher-Schick, A., Pohl, M., Schmiegel, W.[2015]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

The future development of bevacizumab in colorectal cancer. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Expanding the clinical development of bevacizumab. [2019]

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

Bevacizumab. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Phase IV study of bevacizumab in combination with infusional fluorouracil, leucovorin and irinotecan (FOLFIRI) in first-line metastatic colorectal cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Managing patients treated with bevacizumab combination therapy. [2015]

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

Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Incidence and management of bevacizumab-related toxicities in colorectal cancer. [2022]

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

Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. [2021]

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

Adverse events as potential predictive factors of therapeutic activity in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab. [2023]

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

Safety and Clinical Activity of Atezolizumab Plus Bevacizumab in Patients with Ovarian Cancer: A Phase Ib Study. [2021]

12. 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]

13. England pubmed.ncbi.nlm.nih.gov

Drug insight: antiangiogenic therapies for gastrointestinal cancers--focus on monoclonal antibodies. [2015]