Zanidatamab + Chemotherapy for Gastrointestinal Cancers

Recruiting at 25 trial locations

Overseen By Clinical Trial Disclosure & Transparency

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Zymeworks Inc.

Must not be taking: Steroids, Antiseizure medications

Disqualifiers: Brain metastases, Cardiac disease, others

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

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: Unknown

Duration: Up to 11 months

74 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are on certain cancer treatments or have specific health conditions, you may not be eligible to participate.

What data supports the effectiveness of the drug combination Zanidatamab + Chemotherapy for gastrointestinal cancers?

Research shows that combining drugs like cisplatin and 5-fluorouracil (5-FU) with other agents can improve survival in gastric cancer patients. Capecitabine, a form of 5-FU, has been effective in combination with cisplatin and other drugs, offering a convenient oral option with similar effectiveness to intravenous 5-FU. ^{1 2 3 4 5}

What is the safety profile of Zanidatamab and chemotherapy for gastrointestinal cancers?

Bevacizumab, a drug often used in combination with chemotherapy, has a safety profile that includes mild to moderate side effects like high blood pressure, protein in urine, and minor bleeding, which are generally manageable. More serious side effects like wound healing issues, gastrointestinal perforations, and arterial thrombosis are less common. This makes it a suitable addition to chemotherapy in cases where it has been shown to be effective. ^{6 7 8 9 10}

What makes the drug Zanidatamab + Chemotherapy unique for gastrointestinal cancers?

Zanidatamab, combined with chemotherapy, is unique because it targets specific proteins on cancer cells, potentially enhancing the effectiveness of traditional chemotherapy drugs like 5-FU, cisplatin, and oxaliplatin. This combination aims to improve outcomes in gastrointestinal cancers, where no standard chemotherapy regimen has been established. ^{4 11 12 13 14}

What is the purpose of this trial?

This is a multicenter, global, Phase 2, open-label, 2-part, first-line study to investigate the safety, tolerability, and anti-tumor activity of ZW25 (zanidatamab) plus standard first-line combination chemotherapy regimens for selected gastrointestinal (GI) cancers. Eligible patients include those with unresectable, locally advanced, recurrent or metastatic HER2-expressing gastroesophageal adenocarcinoma (GEA), biliary tract cancer (BTC), or colorectal cancer (CRC).

Research Team

Phillip Garfin, MD, PhD

Principal Investigator

Jazz Pharmaceuticals

Eligibility Criteria

This trial is for adults with advanced HER2-expressing gastrointestinal cancers, including gastroesophageal adenocarcinoma, biliary tract cancer, and colorectal cancer that can't be removed by surgery. Participants should have an ECOG score of 0 or 1 (which means they are fully active or restricted in physically strenuous activity but can do light work), no prior treatment with HER2-targeted agents, and no significant heart disease or untreated brain metastases.

Inclusion Criteria

My condition meets the criteria outlined in Part 1.

My bile duct cancer is advanced and cannot be removed by surgery, and it tests positive for HER2.

My heart's left ventricle is functioning well.

Exclusion Criteria

I have been treated with a HER2-targeted therapy before.

I haven't had cancer treatment recently, except for early-stage therapy over 6 months ago.

I have treated brain metastases and have been stable without steroids or seizure meds for 1 month.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ZW25 plus standard first-line combination chemotherapy regimens for selected gastrointestinal cancers

Up to 11 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Treatment Details

Interventions

• Bevacizumab
• Capecitabine
• Cisplatin
• Fluorouracil
• Gemcitabine
• Leucovorin
• Oxaliplatin
• ZW25 (Zanidatamab)

Trial Overview The study tests ZW25 (zanidatamab) combined with standard chemotherapy to see how safe it is and how well it works against certain gastrointestinal cancers. It's a Phase 2 trial where all participants receive the experimental drug plus one of several chemo regimens like Fluorouracil/Leucovorin with Bevacizumab or Gemcitabine/Cisplatin.

Participant Groups

Group I: ZW25 + mFOLFOX6 with bevacizumab Experimental Treatment 5 Interventions

ZW25 plus 5-FU, leucovorin, oxaliplatin, and bevacizumab

Group II: ZW25 + mFOLFOX6 Experimental Treatment 4 Interventions

ZW25 plus 5-FU, leucovorin, and oxaliplatin

Group III: ZW25 + XELOX Experimental Treatment 3 Interventions

ZW25 plus capecitabine and oxaliplatin

Group IV: ZW25 + FP Experimental Treatment 3 Interventions

ZW25 plus fluorouracil (5-FU) and cisplatin

Group V: ZW25 + CisGem Experimental Treatment 2 Interventions

ZW25 plus cisplatin and gemcitabine

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?

Zymeworks Inc.

Lead Sponsor

Trials

11

Recruited

2,400+

Jazz Pharmaceuticals

Lead Sponsor

Trials

252

Recruited

35,100+

Bruce C. Cozadd

Jazz Pharmaceuticals

Chief Executive Officer since 2009

BA in Economics from Yale University, MBA from Stanford University

Dr. Austin

Jazz Pharmaceuticals

Chief Medical Officer since 2023

MD from the Royal College of Surgeons in Ireland

Findings from Research

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]

A study of 27 cancer patients with inflammatory bowel disease (IBD) showed that combining bevacizumab with chemotherapy is safe, with no observed clinical flares of IBD during treatment.

Despite some patients experiencing grade 2 or higher complications like proteinuria and hypertension, the overall safety profile suggests that bevacizumab can be effectively used in patients with either quiescent or moderately active IBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Bevacizumab in Cancer Patients with Inflammatory Bowel Disease. Herrera-Gómez, RG., Grecea, M., Gallois, C., et al.[2022]

In a study of 1,401 patients with metastatic colorectal cancer, adding bevacizumab to first-line oxaliplatin-based chemotherapy significantly improved progression-free survival (PFS) from 8.0 months to 9.4 months compared to placebo.

While overall survival was longer in the bevacizumab group (21.3 months vs. 19.9 months), this difference was not statistically significant, indicating that while bevacizumab helps delay disease progression, it may not necessarily extend overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III Study. Saltz, LB., Clarke, S., Díaz-Rubio, E., et al.[2023]

In a phase III study involving patients with metastatic colon cancer, the addition of Ziv-afilbercept to the FOLFIRI regimen significantly improved overall survival (13.5 months vs. 12.06 months) and progression-free survival (6.9 months vs. 4.67 months) compared to FOLFIRI alone.

Ziv-afilbercept was associated with a response rate of 19.8% compared to 11.1% for the control group, but common side effects included diarrhea, fatigue, and hypertension, highlighting the importance of managing its toxicity in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and management of ZIv-aflibercept related toxicities in colorectal cancer. Saif, MW., Relias, V., Syrigos, K., et al.[2020]

In a study involving 1,401 patients with metastatic colorectal cancer, adding bevacizumab to oxaliplatin-based chemotherapy significantly improved progression-free survival (PFS) from 8.0 months to 9.4 months compared to placebo.

While overall survival was slightly better in the bevacizumab group (21.3 months vs. 19.9 months), this difference was not statistically significant, and the response rates were similar between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. Saltz, LB., Clarke, S., Díaz-Rubio, E., et al.[2023]

In Korea, patients with advanced gastric cancer who undergo D2 resection benefit from postoperative adjuvant chemotherapy with S-1 or capecitabine plus oxaliplatin, indicating a potential effective treatment strategy in this population.

Trastuzumab is now part of the standard chemotherapy for gastric cancers that overexpress the HER2 protein, highlighting the importance of targeted therapies in improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for advanced gastric cancer: review and update of current practices. Park, SC., Chun, HJ.[2023]

Chemotherapy significantly increases survival and improves quality of life in patients with advanced gastric carcinoma compared to supportive measures alone.

Current standard treatments include infusional 5-FU combined with cisplatin or ECF, while newer third-generation combinations with taxanes and irinotecan show similar effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Patient with stomach cancer with metastases. What is the value of chemotherapy?]. Wilke, H., Stahl, M., Vanhoefer, U.[2013]

Combination chemotherapy regimens, such as FAMTX and ECF, show promising response rates in treating locally advanced and metastatic gastric adenocarcinomas, but they come with significant toxicity.

While chemotherapy has been shown to improve overall survival and quality of life compared to best supportive care, adjuvant chemotherapy after surgery has not demonstrated a survival benefit, and the effectiveness of preoperative chemotherapy remains uncertain pending further randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy of gastric cancer. Schipper, DL., Wagener, DJ.[2019]

Pemetrexed shows promising efficacy in treating gastrointestinal tumors, with a 15-17% response rate in metastatic colorectal cancer and a 6% response rate in advanced pancreatic cancer, comparable to standard treatments like gemcitabine.

The drug has a generally mild side effect profile, especially when combined with folate supplementation and dexamethasone, indicating potential for further studies to explore its role in combination therapies for colorectal, pancreatic, and gastric cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pemetrexed in patients with gastrointestinal carcinoma. de Gramont, A., Kindler, HL.[2019]

References

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

Advanced gastric cancer: an update and future directions. [2021]

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

A phase II study of capecitabine, oxaliplatin, and bevacizumab in the treatment of metastatic esophagogastric adenocarcinomas. [2022]

3. Greece pubmed.ncbi.nlm.nih.gov

Cisplatin Plus Capecitabine After Adjuvant S-1 in Metastatic Gastric Cancer: A Phase II T-CORE1102 Trial. [2022]

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

[Neo-adjuvants, adjuvants and palliative therapy for gastric carcinoma]. [2008]

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

Emerging role of capecitabine in gastric cancer. [2022]

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

Managing patients treated with bevacizumab combination therapy. [2015]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Bevacizumab in Cancer Patients with Inflammatory Bowel Disease. [2022]

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

Bevacizumab in Combination With Oxaliplatin-Based Chemotherapy As First-Line Therapy in Metastatic Colorectal Cancer: A Randomized Phase III Study. [2023]

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

Incidence and management of ZIv-aflibercept related toxicities in colorectal cancer. [2020]

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

Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. [2023]

11. Korea (South) pubmed.ncbi.nlm.nih.gov

Chemotherapy for advanced gastric cancer: review and update of current practices. [2023]

12. Germany pubmed.ncbi.nlm.nih.gov

[Patient with stomach cancer with metastases. What is the value of chemotherapy?]. [2013]

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

Chemotherapy of gastric cancer. [2019]

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

Pemetrexed in patients with gastrointestinal carcinoma. [2019]