Study to Assess Adverse Events and Pharmacokinetics in Adult Participants With Non-Small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma and Other Solid Tumors, Receiving Intravenous Infusion of Azirkitug Alone or in Combination(s) With Budigalimab, Bevacizumab, or Telisotuzumab Adizutecan

Official title

A Global First-in-Human Study in NSCLC, HNSCC, and Solid Tumors With Azirkitug as a Single Agent and in Combination(s) With Budigalimab, Bevacizumab, or Telisotuzumab Adizutecan

Overview

Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. Non-Small Cell Lung Cancer (NSCLC) is a solid tumor, a disease in which cancer cells form in the tissues of the lung. Head and Neck Squamous Cell Carcinoma (HNSCC) is a solid tumor, a disease in which cancer cells form in the tissues of the head and neck. The purpose of this study is to assess adverse events and pharmacokinetics of azirkitug as a monotherapy and in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan. Bevacizumab is an approved product, while budigalimab, azirkitug, and telisotuzumab adizutecan are investigational drugs being developed for the treatment of NSCLC, HNSCC, and other solid tumors. Study doctors put the participants in groups called treatment arms. The maximum-tolerated dose (MTD)/maximum administered dose (MAD) of azirkitug will be explored. Each treatment arm receives a different dose of azirkitug in monotherapy and in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan. Approximately 694 adult participants will be enrolled in the study across approximately 80 sites worldwide. Participants will receive azirkitug as a monotherapy or in combination with budigalimab, bevacizumab, or telisotuzumab adizutecan as an Intravenous (IV) Infusion for an estimated treatment period of up to 2 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Interventions

• Drug Azirkitug
  Intravenous (IV) Infusion
• Drug Budigalimab
  Intravenous (IV) Infusion
• Drug Bevacizumab
  Intravenous (IV) Infusion
• Drug Telisotuzumab Adizutecan
  Intravenous (IV) Infusion

Primary outcome measures

• Number of Participants with Adverse Events (AE) [Time frame: Up to 2 Years]
• Maximum Observed Serum Concentration (Cmax) of Azirkitug [Time frame: Up to 2 Years]
• Time to Maximum Observed Serum Concentration (Tmax) of Azirkitug [Time frame: Up to 2 Years]
• Terminal Elimination Half-Life (t1/2) of Azirkitug [Time frame: Up to 2 Years]
• Area Under the Serum Concentration Versus Time Curve (AUC) of Azirkitug [Time frame: Up to 2 Years]
• Azirkitug Antidrug Antibody (ADA) [Time frame: Up to 2 Years]
• Azirkitug Neutralizing Antidrug Antibody (nADA) [Time frame: Up to 2 Years]
• Cmax of Budigalimab [Time frame: Up to 2 Years]
• Tmax of Budigalimab [Time frame: Up to 2 Years]
• t1/2 of Budigalimab [Time frame: Up to 2 Years]

Eligibility criteria

Inclusion criteria

• Pre Treatment biopsy or archive tissue within 6 months without intervening treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of <= 0 or 1 and a life expectancy of >= 3 months.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
• Laboratory values meeting criteria outlined in the protocol
• NSCLC - Advanced or metastatic progressed on standard of care (SOC) including chemotherapy and prior anti-PD-(L)1 antibody (separately or in combination). Actionable gene alterations are eligible if failed targeted therapeutic options.
• HSNCC - Advanced/metastatic progressed on platinum and PD-1/PD-LI in recurrent or metastatic setting.
• Micro Satellite Stable Colorectal Cancer (MSS-CRC) - Progressed on Oxaliplatin, Irinotecan, a fluoropyrimidine, anti-EGFR, VEGF or VEGFR therapies, BRAFV600E or HER2, other targetable mutations targeted with locally approved therapy, TAS-102, Regorafenib and not MSI-h or MMR-deficient
• Gastric and Gastroesophageal Junction adenocarcinoma (GEA) - Advanced/metastatic progressed on at least 1 prior cytotoxic chemotherapeutic regimen and if applicable immune checkpoint inhibitor and/or HER2 therapy
• High-Grade Serous Ovarian Cancer (HGSOC) - Progressed serous epithelial ovarian, fallopian tube or primary peritoneal cancer post SOC and not eligible for surgical resection. Platinum resistant cannot have >5 lines of prior therapy.
• Pancreatic Adenocarcinoma (PDAC) - Advanced/metastatic progressed after SOC. Includes adenosquamous carcinoma and post-Whipple.
• Triple Negative Breast Cancer (TNBC) - Progressed after 1 or 2 systemic therapy that must have included taxane and treatment naïve to immunotherapy targeting T-cell co-stimulation

Exclusion criteria

• Pancreatic Ductal Adenocarcinoma (PDAC) - Excludes neuroendocrine or acinar pancreatic carcinoma and participants with coagulopathy or at risk of or history of Deep vein thrombosis (DVT)/PE
• No major surgery within 28 days prior to dosing
• No active autoimmune/immunodeficiency disease with limited exceptions
• Combination treatment excludes participants treated with anti-programmed cell death protein 1(PD-1)/Programmed cell death ligand 1 (PD-L1) who had immune mediated toxicity G3 or greater, interstitial lung disease, or hypersensitivity Combination treatment may also require no significant cardiac deficiencies and/or events
• Pregnancy
• Excluded medications include anticancer therapy within 5 half-live or 28 days (whichever is shorter), agent targeting Chemokine Receptor (CCR)8, live vaccines, immunosuppressive medication with limited exceptions

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 20 centers

• City of Hope National Medical Center /ID# 276272 — Duarte
• City of Hope - Orange County Lennar Foundation Cancer Center /ID# 278589 — Irvine
• USC Norris Comprehensive Cancer Center /ID# 279603 — Los Angeles
• University of Illinois Hospital and Health Sciences System /ID# 251750 — Chicago
• University of Chicago Medical Center /ID# 276271 — Chicago
• Fort Wayne Medical Oncology and Hematology, Inc /ID# 232593 — Fort Wayne
• Community Health Network, Inc. /ID# 243011 — Indianapolis
• Norton Cancer Institute /ID# 248903 — Louisville
• … and 12 more centers

Israel · 8 centers

• Shamir Medical Center /ID# 276238 — Beer Ya'akov
• Meir Medical Center /ID# 277327 — Kefar Sava
• Rabin Medical Center. /ID# 250497 — Petah Tikva
• The Chaim Sheba Medical Center /ID# 238332 — Ramat Gan
• Tel Aviv Sourasky Medical Center /ID# 276591 — Tel Aviv
• Rambam Health Care Campus /ID# 238333 — Haifa
• Shaare Zedek Medical Center /ID# 276244 — Jerusalem
• Hadassah Medical Center-Hebrew University /ID# 252287 — Jerusalem

Japan · 7 centers

• Aichi Cancer Center Hospital /ID# 250405 — Nagoya
• National Cancer Center Hospital East /ID# 238840 — Kashiwa-shi
• Kobe University Hospital /ID# 250409 — Kobe
• Kansai Medical University Hospital /ID# 276805 — Hirakata-shi
• Shizuoka Cancer Center /ID# 250408 — Sunto-gun
• National Cancer Center Hospital /ID# 238372 — Chuo-ku
• Wakayama Medical University Hospital /ID# 276806 — Wakayama

South Korea · 5 centers

• National Cancer Center /ID# 252290 — Goyang-si
• CHA Bundang Medical Center /ID# 252291 — Seongnam
• Yonsei University Health System Severance Hospital /ID# 252288 — Seoul
• Asan Medical Center /ID# 252289 — Seoul
• The Catholic University of Korea, Seoul St. Marys Hospital /ID# 252867 — Seoul

Taiwan · 5 centers

• Taipei Medical University Shuang Ho Hospital /ID# 252449 — New Taipei City
• National Cheng Kung University Hospital /ID# 252262 — Tainan
• National Taiwan University Hospital /ID# 251894 — Taipei
• Taipei Medical University Hospital /ID# 252450 — Taipei
• Tri-Service General Hospital /ID# 252263 — Taipei

Canada · 3 centers

• Tom Baker Cancer Centre /ID# 276206 — Calgary
• Princess Margaret Cancer Centre /ID# 276275 — Toronto
• Centre Hospitalier de l'Universite de Montreal (CHUM) /ID# 276274 — Montreal

Identifiers

NCT: NCT05005403 · M21-410

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗