Clinical trial NCT05462873: A Study to Investigate the Safety and Tolerability of Intravenous QEQ278 in Patients With Advanced Solid Tumors
Official title: A Phase I/Ib, Open-label, Multi-center, Study of QEQ278 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Carcinoma, Renal Cell
Esophageal Squamous Cell Carcinoma
Squamous Cell Carcinoma of Head and Neck
Keywords: NKG2D
NKG2D-L
immunotherapy
ADCC
NK cells
NSCLC
ESCC
RCC
HPV-associated HNSCC
QEQ278
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-07-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence and nature of Dose Limiting Toxicities (DLTs) during the DLT evaluation period for single agent QEQ278
timeFrame: 28 days
measure: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Up to 31 months
measure: Frequency of dose interruptions, reductions
timeFrame: Up to 30 months
measure: Dose intensity
timeFrame: Up to 30 months
Secondary outcomes:
measure: Overall response rate (ORR) per RECIST v1.1
timeFrame: Up to 30 months
measure: Disease control rate (DCR) per RECIST v1.1
timeFrame: Up to 30 months
measure: Duration of Response (DOR) per RECIST v1.1
timeFrame: Up to 30 months
measure: Progression-free survival (PFS) per RECIST v 1.1
timeFrame: Up to 30 months
measure: Peak serum concentration (Cmax) of QEQ278
timeFrame: During first 168 days of treatment
measure: Area under the concentration time curve (AUC) last of QEQ278
timeFrame: During first 168 days of treatment
measure: Area under the concentration time curve (AUC) infinity of QEQ278
timeFrame: During first 168 days of treatment
measure: Time to reach peak serum concentration (Tmax) of QEQ278
timeFrame: During first 168 days of treatment
measure: Elimination half-life (T1/2) of QEQ278
timeFrame: During first 168 days of treatment
measure: Total body clearance (CL) of QEQ278
timeFrame: During first 168 days of treatment
measure: Volume of distribution (Vz) of QEQ278
timeFrame: During first 168 days of treatment
measure: Incidence of anti-drug antibody (ADA)
timeFrame: Day 1 and 15
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California LA
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital Dept. of Mass General Hospital
state: Massachusetts
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
Study officials:
References: