Zanidatamab + Chemotherapy for Gastrointestinal Cancers

No longer recruiting at 31 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, zanidatamab (an experimental therapy), combined with standard chemotherapy, to determine its effectiveness against certain gastrointestinal cancers. The goal is to assess the safety and efficacy of this combination for cancers that are difficult to remove surgically, such as specific types of stomach, bile duct, and colorectal cancers that express the HER2 protein. Individuals with these cancers, which have spread or returned and cannot be surgically removed, may qualify for this trial if they have not received certain prior treatments. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that zanidatamab (ZW25) combined with chemotherapy is generally safe and well-tolerated. Reports indicate that when zanidatamab was used with treatments like mFOLFOX6 (a mix of cancer drugs) and bevacizumab (a drug that helps stop cancer growth), the safety profile was manageable, with side effects that were usually not severe.

When combined with FP (fluorouracil and cisplatin) and with CisGem (cisplatin and gemcitabine), zanidatamab resulted in similar safety levels. The side effects were considered manageable and could be controlled with proper care.

For those who received zanidatamab with XELOX (capecitabine and oxaliplatin), the safety was also acceptable, with generally manageable side effects. This aligns with results seen in other combinations studied.

While these combinations are still under investigation and not fully approved for all uses, the current phase of the study suggests that the treatment is safe enough to continue testing in humans. Always consult healthcare providers to understand what these findings mean for health decisions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Zanidatamab because, unlike existing treatments for gastrointestinal cancers, it is a bispecific antibody targeting two different sites on the HER2 receptor. This dual-targeting approach can potentially lead to more effective tumor inhibition compared to traditional HER2 therapies like trastuzumab, which only targets a single site. Additionally, Zanidatamab is being tested in combination with various chemotherapy regimens, which may enhance its effectiveness and offer a new approach for patients who do not respond well to current treatments. This innovative mechanism of action represents a promising advancement in tackling tough-to-treat gastrointestinal cancers.

What evidence suggests that this trial's treatments could be effective for gastrointestinal cancers?

Research shows that zanidatamab, a treatment in this trial, has promising results for certain gastrointestinal cancers when combined with various chemotherapy treatments. Participants in this trial may receive zanidatamab with chemotherapy regimens such as mFOLFOX6, FP, XELOX, or CisGem, with or without bevacizumab. For HER2-positive metastatic colorectal cancer, studies have found that combining zanidatamab with chemotherapy, with or without bevacizumab, allowed patients to live without cancer progression for an average of 15.2 months. In another study, 76.2% of gastroesophageal cancer patients responded to the treatment, with the response lasting an average of 18.7 months. For biliary tract cancer, zanidatamab led to an average of 6.7 months without cancer progression and a 65% response rate. These findings suggest that zanidatamab could effectively treat patients with HER2-positive gastrointestinal cancers. ^{1 3 6 7 8}

Who Is on the Research Team?

Phillip Garfin, MD, PhD

Principal Investigator

Jazz Pharmaceuticals

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03929666

NCT03929666 | A Safety and Efficacy Study of ZW25 ... 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 ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0959804925002138

Real-world efficacy of zanidatamab in patients with HER2 ... Zanidatamab demonstrated benefit in HER2-positive BTC in real-world patients. Zanidatamab showed a median PFS of 6.7 months and ORR of 65%.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.TPS648

HERIZON-BTC-302: A phase 3 study of zanidatamab with ... Confirmed objective response rate (cORR) was 41.3% with rapid and durable responses and a manageable safety profile. This phase 3 trial is ...

4. ccanewsonline.com ccanewsonline.com/special-issues/2021-year-in-review-cca/zanidatamab-zw25-in-her2-positive-biliary-tract-cancers-results-from-a-phase-1-study

Zanidatamab (ZW25) in HER2-Positive Biliary Tract Cancers Of the 17 patients who were evaluable for response, the confirmed overall response rate was 47% (n = 8), all of which were partial responses. Five additional ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06282575

NCT06282575 | Efficacy and Safety of Zanidatamab With ... The purpose of this study is to evaluate the efficacy and safety of Zanidatamab plus CisGem (Cisplatin and Gemcitabine) with or without the addition of a ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00537-X/fulltext

319P Antitumour activity and safety of first-line ... In this phase 2 study, zani + CisGem demonstrated promising preliminary antitumour activity with a manageable safety profile for 1L treatment of pts with HER2- ...

7. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00287-6/abstract

Zanidatamab plus chemotherapy as first-line treatment for ... Randomized, phase II study of trastuzumab beyond progression in patients with HER2-positive advanced gastric or gastroesophageal junction cancer.

8. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03929666/

Clinical Trial: NCT03929666 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 ( ...