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

Primary Purpose

Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell, Esophageal Squamous Cell Carcinoma

Status

Recruiting

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

QEQ278

About this trial

This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung focused on measuring NKG2D, NKG2D-L, immunotherapy, ADCC, NK cells, NSCLC, ESCC, RCC, HPV-associated HNSCC, QEQ278

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of California Los Angeles Santa Monica LocationRecruiting
Massachusetts General Hospital Dept. of Mass General HospitalRecruiting
Novartis Investigative SiteRecruiting
Novartis Investigative SiteRecruiting
Novartis Investigative SiteRecruiting
Novartis Investigative SiteRecruiting
Novartis Investigative SiteRecruiting
Novartis Investigative SiteRecruiting
Novartis Investigative SiteRecruiting
Novartis Investigative SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Part 1: Dose escalation

Part 2: Dose expansion

Arm Description

Dose escalation with QEQ278 single agent

Dose expansion with QEQ278 single agent

Outcomes

Primary Outcome Measures

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.

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.

Frequency of dose interruptions, reductions

Number of dose interruptions of QEQ278 and number of dose reductions of QEQ278

Dose intensity

Dose intensity of QEQ278 is defined as the ratio of actual cumulative dose received and actual duration of exposure.

Secondary Outcome Measures

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.

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.

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.

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.

Peak serum concentration (Cmax) of QEQ278

The maximum (peak) serum drug concentration after single dose administration

Area under the concentration time curve (AUC) last of QEQ278

The AUC from time zero to the last measurable concentration sampling time

Area under the concentration time curve (AUC) infinity of QEQ278

The AUC from time zero to infinity

Time to reach peak serum concentration (Tmax) of QEQ278

The time to reach maximum (peak) serum drug concentration after single dose administration

Elimination half-life (T1/2) of QEQ278

The elimination half-life associated with the terminal slope of a semi logarithmic concentration-time curve

Total body clearance (CL) of QEQ278

The total body clearance of drug from the serum

Volume of distribution (Vz) of QEQ278

The apparent volume of distribution during terminal phase

Incidence of anti-drug antibody (ADA)

Immunogenicity of QEQ278

Full Information

NCT ID

NCT05462873

First Posted

July 14, 2022

Last Updated

August 31, 2023

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT05462873

Brief Title

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

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

April 4, 2023 (Actual)

Primary Completion Date

April 13, 2026 (Anticipated)

Study Completion Date

April 13, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

125 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Part 1: Dose escalation

Arm Type

Experimental

Arm Description

Dose escalation with QEQ278 single agent

Arm Title

Part 2: Dose expansion

Arm Type

Experimental

Arm Description

Dose expansion with QEQ278 single agent

Intervention Type

Biological

Intervention Name(s)

QEQ278

Intervention Description

Intravenous dosing of QEQ278

Primary Outcome Measure Information:

Title

Incidence and nature of Dose Limiting Toxicities (DLTs) during the DLT evaluation period for single agent QEQ278

Description

Time Frame

28 days

Title

Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

Description

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.

Time Frame

Up to 31 months

Title

Frequency of dose interruptions, reductions

Description

Number of dose interruptions of QEQ278 and number of dose reductions of QEQ278

Time Frame

Up to 30 months

Title

Dose intensity

Description

Dose intensity of QEQ278 is defined as the ratio of actual cumulative dose received and actual duration of exposure.

Time Frame

Up to 30 months

Secondary Outcome Measure Information:

Title

Overall response rate (ORR) per RECIST v1.1

Description

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.

Time Frame

Up to 30 months

Title

Disease control rate (DCR) per RECIST v1.1

Description

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.

Time Frame

Up to 30 months

Title

Duration of Response (DOR) per RECIST v1.1

Description

Time Frame

Up to 30 months

Title

Progression-free survival (PFS) per RECIST v 1.1

Description

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.

Time Frame

Up to 30 months

Title

Peak serum concentration (Cmax) of QEQ278

Description

The maximum (peak) serum drug concentration after single dose administration

Time Frame