Trial record 1 of 1 for:
zwi-zw25-201
A Safety and Efficacy Study of ZW25 (Zanidatamab) Plus Combination Chemotherapy in HER2-expressing Gastrointestinal Cancers, Including Gastroesophageal Adenocarcinoma, Biliary Tract Cancer, and Colorectal Cancer
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| ClinicalTrials.gov Identifier: NCT03929666 |
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Recruitment Status :
Recruiting
First Posted : April 29, 2019
Last Update Posted : March 6, 2023
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Sponsor:
Zymeworks Inc.
Information provided by (Responsible Party):
Zymeworks Inc.
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Brief Summary:
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).
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| HER2-expressing Gastrointestinal Cancers, Including Gastroesophageal Adenocarcinoma, Biliary Tract Cancer, and Colorectal Cancer | Drug: ZW25 (Zanidatamab) Drug: Capecitabine Drug: Cisplatin Drug: Fluorouracil Drug: Leucovorin Drug: Oxaliplatin Drug: Bevacizumab Drug: Gemcitabine | Phase 2 |
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
Part 1 of the study will first evaluate the safety and tolerability of ZW25 plus standard first-line combination chemotherapy (XELOX, FP, or mFOLFOX6 for GEA; mFOLFOX6 with or without bevacizumab for CRC; and CisGem for BTC) and will confirm the recommended dosage (RD) of ZW25 when administered in combination with each of these multi-agent chemotherapy regimens. Then, Part 2 of the study will evaluate the anti-tumor activity of ZW25 plus combination chemotherapy in HER2-expressing GEA, BTC, and CRC.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 362 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase 2 Study of ZW25 Plus First-line Combination Chemotherapy in HER2-Expressing Gastrointestinal (GI) Cancers, Including Gastroesophageal Adenocarcinoma (GEA), Biliary Tract Cancer (BTC), and Colorectal Cancer (CRC) |
| Actual Study Start Date : | August 29, 2019 |
| Estimated Primary Completion Date : | March 31, 2023 |
| Estimated Study Completion Date : | April 30, 2024 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: ZW25 + FP
ZW25 plus fluorouracil (5-FU) and cisplatin
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Drug: ZW25 (Zanidatamab)
Drug: Cisplatin Administered IV Drug: Fluorouracil Administered IV |
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Experimental: ZW25 + mFOLFOX6
ZW25 plus 5-FU, leucovorin, and oxaliplatin
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Drug: ZW25 (Zanidatamab)
Drug: Fluorouracil Administered IV Drug: Leucovorin Administered IV Drug: Oxaliplatin Administered IV |
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Experimental: ZW25 + XELOX
ZW25 plus capecitabine and oxaliplatin
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Drug: ZW25 (Zanidatamab)
Drug: Capecitabine Administered orally twice daily (PO bid) Drug: Oxaliplatin Administered IV |
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Experimental: ZW25 + mFOLFOX6 with bevacizumab
ZW25 plus 5-FU, leucovorin, oxaliplatin, and bevacizumab
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Drug: ZW25 (Zanidatamab)
Drug: Fluorouracil Administered IV Drug: Leucovorin Administered IV Drug: Oxaliplatin Administered IV Drug: Bevacizumab Administered IV |
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Experimental: ZW25 + CisGem
ZW25 plus cisplatin and gemcitabine
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Drug: Cisplatin
Administered IV Drug: Gemcitabine Administered IV |
Primary Outcome Measures :
- Incidence of dose-limiting toxicities (DLTs) (Part 1) [ Time Frame: Up to 6 weeks ]Number of participants who experienced a DLT. DLTs include adverse events considered to be related to study treatment, including the evaluated dose level of ZW25, any component or combination of the components of a chemotherapy regimen, or the combination of ZW25 plus a chemotherapy regimen.
- Incidence of adverse events (Part 1) [ Time Frame: Up to 11 months ]Number of participants who experienced an adverse event
- Incidence of lab abnormalities (Part 1) [ Time Frame: Up to 11 months ]Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology and chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
- Objective response rate (ORR) (Part 2) [ Time Frame: Up to 10 months ]Number of participants who achieved a best response of either complete response (CR) or partial response (PR) during treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Secondary Outcome Measures :
- Objective response rate (ORR) (Part 1) [ Time Frame: Up to 10 months ]Number of participants who achieved a best response of either CR or PR during treatment per RECIST 1.1
- Disease control rate (Parts 1 and 2) [ Time Frame: Up to 10 months ]Number of participants who achieved a best response of CR, PR, or stable disease (SD) during treatment per RECIST 1.1
- Duration of response (Parts 1 and 2) [ Time Frame: Up to 2 years ]Median duration of response (in months) and range (minimum, maximum)
- Clinical benefit rate (Parts 1 and 2) [ Time Frame: Up to 2 years ]Number of participants with SD for ≥ 24 weeks or a confirmed, best overall response of CR or PR per RECIST 1.1
- Progression-free survival (Parts 1 and 2) [ Time Frame: Up to 2 years ]Median progression-free survival (in months) and range (minimum, maximum)
- Overall survival (Parts 1 and 2) [ Time Frame: Up to 2 years ]Median overall survival (in months) and range (minimum, maximum)
- Incidence of anti-drug antibodies (ADAs) (Parts 1 and 2) [ Time Frame: Up to 11 months ]Number of participants who develop ADAs
- End of infusion concentration of ZW25 (Parts 1 and 2) [ Time Frame: Up to 11 months ]
- Maximum serum concentration of ZW25 (Parts 1 and 2) [ Time Frame: Up to 11 months ]
- Trough concentration of ZW25 (Parts 1 and 2) [ Time Frame: Up to 11 months ]
- Incidence of adverse events (Part 2) [ Time Frame: Up to 11 months ]Number of participants who experienced an adverse event
- Incidence of lab abnormalities (Part 2) [ Time Frame: Up to 11 months ]Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology and chemistry. Grades are defined using National Cancer Institute's CTCAE, version 5.0.
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion:
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Disease diagnosis:
- Part 1:
- GEA: Unresectable, locally advanced, recurrent or metastatic HER2-expressing GEA (IHC 3+ or 2+ with or without gene amplification based upon local assessment or central assessment)
- BTC: Unresectable, locally advanced, recurrent or metastatic HER2-expressing BTC (including intrahepatic cholangiocarcinoma [ICC], extrahepatic cholangiocarcinoma [ECC], or gallbladder cancer [GBC]) (IHC 3+ with or without gene amplification; or IHC 0, 1+ or 2+ with gene amplification, based upon central assessment)
- CRC: Unresectable, locally advanced, recurrent or metastatic HER2-expressing CRC (IHC 3+ with or without gene amplification; or IHC 0, 1+ or 2+ with gene amplification, based upon central assessment). Patients will be required to be extended RAS (KRAS and NRAS) and BRAF wild-type based upon central assessment.
- Part 2:
- GEA: Unresectable, locally advanced, recurrent or metastatic HER2-expressing GEA (IHC 3+, or IHC 2+ and FISH+ by central assessment)
- BTC: Same as Part 1
- CRC: Same as Part 1
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Tumor measurements as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1:
- Part 1: Measurable or non-measurable disease
- Part 2: Measurable disease
- An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
- Adequate organ function
- Adequate cardiac left ventricular function, as defined by a LVEF >/= institutional standard of normal
Exclusion:
- Prior treatment with a HER2-targeted agent
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Prior systemic anti-cancer therapy (including investigational products) except prior adjuvant/neoadjuvant therapy, which must be completed at least 6 months prior to first study treatment dosing. For subjects with BTC and CRC the following additional exceptions apply:
- BTC: patients may have started therapy for advanced disease but may not have received more than one cycle of any standard gemcitabine-based chemotherapy regimen.
- CRC: patients may have started therapy for advanced disease but may not have received more than one cycle of 5-FU-based chemotherapy (< 1 month of therapy).
- Patients with certain contraindications to bevacizumab cannot be enrolled on the mFOLFOX6-2 with bevacizumab arm.
- Palliative radiotherapy is allowed if completed at least 2 weeks prior to first study treatment dosing
- Untreated known brain metastases (patients with treated brain metastases who are off steroids, off antiseizure medications, and stable for at least 1 month at the time of screening are eligible)
- Clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension or any history of symptomatic congestive heart failure (CHF). Patients with known myocardial infarction or unstable angina within 6 months prior to randomization are also excluded.
- QTc Fridericia (QTcF) > 470 ms. For patients with longer QTcF on initial electrocardiogram (ECG), follow-up ECG may be performed in triplicate to determine eligibility
- Peripheral neuropathy > Grade 1 per NCI-CTCAE v5.0
- Clinically significant interstitial lung disease
- Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
- Active hepatitis B or hepatitis C infection or infection with Human Immunodeficiency Virus (HIV)-1 or HIV-2 (Exception: patients with well controlled HIV [e.g., CD4 > 350/mm3 and undetectable viral load] are eligible)
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03929666
Contacts
| Contact: Zymeworks Clinical Trial Resource | (206) 237-1030 | medinfo@zymeworks.com |
Locations
Show 21 study locations
Sponsors and Collaborators
Zymeworks Inc.
Investigators
| Study Director: | Rajen Oza, MD | Zymeworks BC Inc. |
| Responsible Party: | Zymeworks Inc. |
| ClinicalTrials.gov Identifier: | NCT03929666 |
| Other Study ID Numbers: |
ZWI-ZW25-201 |
| First Posted: | April 29, 2019 Key Record Dates |
| Last Update Posted: | March 6, 2023 |
| Last Verified: | February 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Zymeworks Inc.:
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HER2 Bispecific antibody Biparatopic antibody Immunotherapy Gastric cancers Esophageal cancers Gastroesophageal junction (GEJ) cancers Chemotherapy FP mFOLFOX6 Capecitabine Cisplatin |
5-FU Leucovorin (folinic acid) Oxaliplatin XELOX Gastrointestinal cancers Gastroesophageal adenocarcinoma Biliary tract cancer Colorectal cancer Intrahepatic cholangiocarcinoma Extrahepatic cholangiocarcinoma Gall bladder |
Additional relevant MeSH terms:
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Colorectal Neoplasms Adenocarcinoma Biliary Tract Neoplasms Gastrointestinal Neoplasms Intestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Carcinoma Neoplasms, Glandular and Epithelial |
Neoplasms by Histologic Type Biliary Tract Diseases Leucovorin Bevacizumab Gemcitabine Fluorouracil Capecitabine Oxaliplatin Antineoplastic Agents, Immunological Antineoplastic Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors |