A Study to Investigate the Safety and Tolerability of Intravenous QEQ278 in Patients With Advanced Solid Tumors

A Phase I/Ib, Open-label, Multi-center, Study of QEQ278 in Patients With Advanced Solid Tumors

To characterize safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of QEQ278 in adult patients with advanced/metastatic non-small cell lung cancer, esophageal squamous cell carcinoma, renal cell carcinoma, and human papilloma virus associated head and neck squamous cell carcinoma.

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung; Squamous Cell Carcinoma of Head and Neck; Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Biological: QEQ278

Detailed Description

This study is an open-label, phase I/Ib, multi-center study of QEQ278 as a single agent, consisting of a dose escalation part followed by a dose expansion part.

In the dose escalation part of the study, patients with non-small cell lung cancer (NSCLC), esophageal squamous cell carcinoma (ESCC), renal cell carcinoma (RCC), or human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) will be treated with QEQ278 single agent until the maximum tolerated dose (MTD) is reached or a lower recommended dose (RD) is established.

The study may enter the dose expansion, after an MTD(s) and/or RD(s) is declared in the dose escalation.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Novartis Investigative Site
• France
  • Paris, France, 75231
    • Novartis Investigative Site
• Germany
  • Essen, Germany, 45147
    • Novartis Investigative Site
• Italy
  • MI
    • Milan, MI, Italy, 20133
      • Novartis Investigative Site
• Japan
  • Chiba
    • Kashiwa, Chiba, Japan, 2778577
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 168583
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08035
    • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California LA
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Dept. of Mass General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study.
• Adult men and women ≥ 18 years of age.
• Histologically confirmed and documented advanced malignancies (locally advanced malignancies, non-curable by surgery or radiotherapy and metastatic disease). Disease must be measurable, including presence of at least one measurable lesion, as determined by RECIST v1.1.
• In the opinion of the treating investigator, patients must have received, but are not benefitting from standard therapies, be intolerant or ineligible to receive such therapy, or have no standard therapy option for the respective disease types (diseases listed below), as well as any other therapies deemed to be standard by local/institutional standard.
• Non-small cell lung cancer
• Esophageal squamous cell carcinoma
• Renal cell carcinoma
• HPV-associated head and neck squamous cell carcinoma
• Must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines. The patient must be willing to undergo a new tumor biopsy at screening and during treatment.

Exclusion Criteria:

• Active previously documented or suspected autoimmune disease. Patients with vitiligo, type I diabetes, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur should not be excluded. Patients previously exposed to anti-PD-1/PD-L1 treatment who are adequately treated for skin rash or with replacement therapy for endocrinopathies should not be excluded.
• Patients with a history of or current interstitial lung disease or pneumonitis ≥ Grade 2.
• Patients who discontinued prior anti-PD-1 therapy due to an anti-PD-1-related toxicity
• Clinically significant cardiac disease or risk factors at screening
• Insufficient bone marrow function at screening:
• Infections:
• Known history of testing positive for Human Immunodeficiency Virus infection.
• Active Hepatitis B and / or Hepatitis C.
• Active, documented COVID-19 infection
• Known history of tuberculosis
• Any serious uncontrolled infection (acute or chronic).
• Systemic chronic steroid therapy (>10 mg/day prednisone or equivalent) or any immunosuppressive therapy, other than replacement-dose steroids in the setting of adrenal insufficiency, within 7 days of the first dose of study treatment. Topical, inhaled, and ophthalmic steroids are allowed.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose escalation; Dose escalation with QEQ278 single agent	Biological: QEQ278; Intravenous dosing of QEQ278
Experimental: Part 2: Dose expansion; Dose expansion with QEQ278 single agent	Biological: QEQ278; Intravenous dosing of QEQ278

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and nature of Dose Limiting Toxicities (DLTs) during the DLT evaluation period for single agent QEQ278	A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the DLT evaluation period and meets the criteria defined in the study protocol.	28 days
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)	Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in laboratory values, vital signs, and electrocardiograms (ECGs) qualifying and reported as AEs.	Up to 31 months
Frequency of dose interruptions, reductions	Number of dose interruptions of QEQ278 and number of dose reductions of QEQ278	Up to 30 months
Dose intensity	Dose intensity of QEQ278 is defined as the ratio of actual cumulative dose received and actual duration of exposure.	Up to 30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) per RECIST v1.1	ORR is defined as the proportion of patients with a confirmed BOR of complete response (CR) or partial response (PR) by local investigator review as per RECIST v1.1.	Up to 30 months
Disease control rate (DCR) per RECIST v1.1	DCR is defined as the proportion of patients with a confirmed best overall response (BOR) of CR or PR or stable disease (SD) by local investigator review as per RECIST v1.1.	Up to 30 months
Duration of Response (DOR) per RECIST v1.1	DOR is defined as the time form the date of the first documented response (CR or PR) to the date of the first documented progression by local investigator review as per RECIST v1.1 or death due to underlying cancer.	Up to 30 months
Progression-free survival (PFS) per RECIST v 1.1	PFS is defined as the time from the date of start of treatment to the date of the first documented progression by local investigator review as per RECIST v1.1, or death due to any cause.	Up to 30 months
Peak serum concentration (Cmax) of QEQ278	The maximum (peak) serum drug concentration after single dose administration	During first 168 days of treatment
Area under the concentration time curve (AUC) last of QEQ278	The AUC from time zero to the last measurable concentration sampling time	During first 168 days of treatment
Area under the concentration time curve (AUC) infinity of QEQ278	The AUC from time zero to infinity	During first 168 days of treatment
Time to reach peak serum concentration (Tmax) of QEQ278	The time to reach maximum (peak) serum drug concentration after single dose administration	During first 168 days of treatment
Elimination half-life (T1/2) of QEQ278	The elimination half-life associated with the terminal slope of a semi logarithmic concentration-time curve	During first 168 days of treatment
Total body clearance (CL) of QEQ278	The total body clearance of drug from the serum	During first 168 days of treatment
Volume of distribution (Vz) of QEQ278	The apparent volume of distribution during terminal phase	During first 168 days of treatment
Incidence of anti-drug antibody (ADA)	Immunogenicity of QEQ278	Day 1 and 15

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2023
• Primary Completion (Actual): January 26, 2026
• Study Completion (Actual): January 26, 2026

Study Registration Dates

• First Submitted: July 14, 2022
• First Submitted That Met QC Criteria: July 14, 2022
• First Posted (Actual): July 18, 2022

Study Record Updates

• Last Update Posted (Actual): February 17, 2026
• Last Update Submitted That Met QC Criteria: February 13, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: immunotherapy; NSCLC; ESCC; NK cells; NKG2D; RCC; ADCC; NKG2D-L; HPV-associated HNSCC; QEQ278
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Lung Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Esophageal Diseases; Lung Neoplasms; Urologic Neoplasms; Carcinoma; Neoplasms, Squamous Cell; Kidney Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Squamous Cell; Esophageal Neoplasms; Squamous Cell Carcinoma of Head and Neck; Esophageal Squamous Cell Carcinoma; Carcinoma, Renal Cell; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: CQEQ278A12101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No