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

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05462873
• Other study ID #: CQEQ278A12101
• Status: Recruiting
• Phase: Phase 1
• Start date: April 4, 2023
• Est. completion date: January 9, 2026

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 125
• Est. completion date: January 9, 2026
• Est. primary completion date: January 9, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Carcinoma, Renal Cell
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Biological:
• QEQ278
Intravenous dosing of QEQ278

Locations

Country	Name	City	State
Belgium	Novartis Investigative Site	Bruxelles
France	Novartis Investigative Site	Paris
Germany	Novartis Investigative Site	Essen
Italy	Novartis Investigative Site	Milano	MI
Japan	Novartis Investigative Site	Kashiwa	Chiba
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Taiwan	Novartis Investigative Site	Taipei
United States	Massachusetts General Hospital Dept. of Mass General Hospital	Boston	Massachusetts
United States	Florida Cancer Specialists Sarasota Office	Fort Myers	Florida
United States	University Of California LA Santa Monica Location	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Italy,  Japan,  Singapore,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Frequency of dose interruptions, reductions	Number of dose interruptions of QEQ278 and number of dose reductions of QEQ278	Up to 30 months
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Peak serum concentration (Cmax) of QEQ278	The maximum (peak) serum drug concentration after single dose administration	During first 168 days of treatment
Secondary	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
Secondary	Area under the concentration time curve (AUC) infinity of QEQ278	The AUC from time zero to infinity	During first 168 days of treatment
Secondary	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
Secondary	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
Secondary	Total body clearance (CL) of QEQ278	The total body clearance of drug from the serum	During first 168 days of treatment
Secondary	Volume of distribution (Vz) of QEQ278	The apparent volume of distribution during terminal phase	During first 168 days of treatment
Secondary	Incidence of anti-drug antibody (ADA)	Immunogenicity of QEQ278	Day 1 and 15