Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Digestive System Diseases

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Adenocarcinoma

Stomach Neoplasms

Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Stomach Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Capecitabine

Vinorelbine

Paclitaxel

Albumin-Bound Paclitaxel

Immunomodulating Agents

Antibodies, Bispecific

Immunoglobulins

Tucatinib

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Protein Kinase Inhibitors

Enzyme Inhibitors

ZW25 administered IV once weekly, once every 2 weeks, or once every 3 weeks. Part 1: in multiple increasing doses; Part 2: ZW25 given at the MTD, OBD, or an RD identified in Part 1; Part 3: ZW25 given at the MTD, OBD, or an RD combined with one of the following selected drug combination:

ZW25 (Zanidatamab)

Combination therapy with ZW25 - Part 3 Treatment Groups 1 and 4

Combination therapy with ZW25 - Part 3 Treatment Groups 2 and 5

Combination therapy with ZW25 - Part 3 Treatment Groups 3 and 6

Combination therapy with ZW25 and Capecitabine - Part 3 Treatment Group 7

Combination therapy with ZW25 - Part 3 Treatment Group 8 (may be opened if recommended by the Safety Monitoring Committee and/or the sponsor)

This is a first-in-human, 3-part study to investigate the safety, tolerability, and effectiveness of ZW25 (zanidatamab) by itself and combined with selected chemotherapy agents in patients with locally advanced (unresectable) and/or metastatic human epidermal growth factor receptor 2 (HER2)-expressing cancers. This study will also the evaluate the way the body absorbs, distributes, and eliminates ZW25 (pharmacokinetics or PK).

Part 1 of the study will evaluate increasing doses of ZW25 to find the highest dose of ZW25 that does not cause unacceptable side effects (maximum-tolerated dose or MTD), the lowest safe dose with the highest rate of effectiveness (optimal biological dose or OBD), and/or other recommended dosages (RDs) of ZW25 in up to 7 dose-specific cohorts. Eligible patients include those with selected HER2-expressing locally advanced (unresectable) and/or metastatic cancers that have progressed after receipt of all therapies known to confer clinical benefit (or ineligible to receive therapy).

Part 2 of the study will further evaluate the safety, tolerability, and efficacy of ZW25 in patients with selected HER2-expressing locally advanced (unresectable) and/or metastatic cancers that have progressed after receipt of all therapies known to confer clinical benefit (or ineligible to receive therapy) in up to 5 separate disease-specific cohorts.

Part 3 of the study will evaluate the safety, tolerability, and efficacy of ZW25 combined with selected chemotherapy agents, including paclitaxel, capecitabine, vinorelbine, or capecitabine and tucatinib. Patients with selected HER2-expressing locally advanced (unresectable) and/or metastatic cancers that have progressed after at least 1 and no more than 3 prior systemic chemotherapy regimens will be evaluated in this part of the study.

Trial of ZW25 (Zanidatamab) in Patients With Advanced HER2-expressing Cancers

Phase I Trial of ZW25 in Patients With Locally Advanced (Unresectable) and/or Metastatic HER2-expressing Cancers

Jazz Pharmaceuticals

Esophageal Neoplasms

Cholangiocarcinoma

Colorectal Neoplasms

Biliary Tract Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Intestinal Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Biliary Tract Diseases

Esophageal Cancer

Bile Duct Cancer

Biliary Tract Cancer

Intrahepatic Cholangiocarcinoma

Micronutrients

Hematinics

Vitamins

Gemcitabine

Bevacizumab

Leucovorin

Fluorouracil

Levoleucovorin

Cisplatin

Oxaliplatin

Folic Acid

Antineoplastic Agents, Immunological

Angiogenesis Inhibitors

Growth Inhibitors

Immunosuppressive Agents

Immunologic Factors

Antidotes

Protective Agents

Vitamin B Complex

Trace Elements

Folinic Acid

Folate

Vitamin B9

ZW25 plus fluorouracil (5-FU) and cisplatin

ZW25 plus 5-FU, leucovorin, and oxaliplatin

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

* Part 1: administered IV at dose levels and schedules determined by the Safety Monitoring Committee (SMC)
* Part 2: RD identified in Part 1

Phillip Garfin, MD, PhD

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).

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.

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

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)

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.

Number of participants who experienced an adverse event

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.

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

Number of participants who achieved a best response of either CR or PR during treatment per RECIST 1.1

Number of participants who achieved a best response of CR, PR, or stable disease (SD) during treatment per RECIST 1.1

Median duration of response (in months) and range (minimum, maximum)

Number of participants with SD for ≥ 24 weeks or a confirmed, best overall response of CR or PR per RECIST 1.1

Median progression-free survival (in months) and range (minimum, maximum)

Median overall survival (in months) and range (minimum, maximum)

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.

Gallbladder Cancer

This multicenter, open-label, single-arm trial will evaluate the anti-tumor activity of ZW25 (zanidatamab) monotherapy in subjects with human epidermal growth factor receptor 2 (HER2)-amplified, inoperable and advanced or metastatic biliary tract cancer (BTC), including intra-hepatic cholangiocarcinoma (ICC), extra-hepatic cholangiocarcinoma (ECC), and gallbladder cancer (GBC).

single-arm, open-label, multi-cohort, multicenter study

A Study of ZW25 (Zanidatamab) in Subjects With Advanced or Metastatic HER2-Amplified Biliary Tract Cancers

A Phase 2b, Open-label, Single-arm Study of ZW25 Monotherapy in Subjects With Advanced or Metastatic HER2-amplified Biliary Tract Cancers

Number of subjects who achieved a confirmed best overall response (BOR) of either complete response (CR) or partial response (PR) during treatment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

The time from the first objective response (CR or PR) to documented progressive disease (PD) per RECIST 1.1, clinical progression, or death from any cause

Proportion of subjects with a DOR ≥ 16 weeks per RECIST 1.1

Number of subjects who achieved a best response of CR, PR, or stable disease (SD) during treatment per RECIST 1.1

The time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1), clinical progression, or death from any cause

Number of subjects who achieved a BOR of either CR or PR during treatment per RECIST 1.1

The time from the first objective response (CR or PR) to documented PD per RECIST 1.1, clinical progression, or death from any cause

Number of subjects who achieved a best response of CR, PR, or SD during treatment per RECIST 1.1

The time from the first dose of study treatment until the date of death from any cause

Number of subjects who experienced AEs or serious adverse events

Number of subjects who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology or chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0

Minimum observed serum concentration (trough)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of ZW25 (Zanidatamab) in Patients With Advanced HER2-expressing Cancers	NCT02892123	HER2-expressing...	ZW25 (Zanidatam... Paclitaxel Capecitabine Vinorelbine Tucatinib Tucatinib	18 Years -	Jazz Pharmaceuticals
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	NCT03929666	HER2-expressing...	ZW25 (Zanidatam... Capecitabine Cisplatin Fluorouracil Leucovorin Oxaliplatin Bevacizumab Gemcitabine	18 Years -	Jazz Pharmaceuticals
Trial of ZW25 (Zanidatamab) in Patients With Advanced HER2-expressing Cancers	NCT02892123	HER2-expressing...	ZW25 (Zanidatam... Paclitaxel Capecitabine Vinorelbine Tucatinib Tucatinib	18 Years -	Jazz Pharmaceuticals
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	NCT03929666	HER2-expressing...	ZW25 (Zanidatam... Capecitabine Cisplatin Fluorouracil Leucovorin Oxaliplatin Bevacizumab Gemcitabine	18 Years -	Jazz Pharmaceuticals
A Study of ZW25 (Zanidatamab) in Subjects With Advanced or Metastatic HER2-Amplified Biliary Tract Cancers	NCT04466891	HER2-amplified ...	ZW25 (Zanidatam...	18 Years -	Jazz Pharmaceuticals

Spots Global Cancer Trial Database for zw25 (zanidatamab)