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

• ClinicalTrials.gov Identifier: NCT05462873
• Recruitment Status: Recruiting
• First Posted: July 18, 2022
• Last Update Posted: April 15, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: July 14, 2022
• First Posted Date: July 18, 2022
• Last Update Posted Date: April 15, 2024
• Actual Study Start Date: April 4, 2023
• Estimated Primary Completion Date: January 9, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 14, 2022)

• Incidence and nature of Dose Limiting Toxicities (DLTs) during the DLT evaluation period for single agent QEQ278 [ Time Frame: 28 days ]
  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) [ Time Frame: Up to 31 months ]
  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 [ Time Frame: Up to 30 months ]
  Number of dose interruptions of QEQ278 and number of dose reductions of QEQ278
• Dose intensity [ Time Frame: Up to 30 months ]
  Dose intensity of QEQ278 is defined as the ratio of actual cumulative dose received and actual duration of exposure.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 14, 2022)

• Overall response rate (ORR) per RECIST v1.1 [ Time Frame: Up to 30 months ]
  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 [ Time Frame: Up to 30 months ]
  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 [ Time Frame: Up to 30 months ]
  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 [ Time Frame: Up to 30 months ]
  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 [ Time Frame: During first 168 days of treatment ]
  The maximum (peak) serum drug concentration after single dose administration
• Area under the concentration time curve (AUC) last of QEQ278 [ Time Frame: During first 168 days of treatment ]
  The AUC from time zero to the last measurable concentration sampling time
• Area under the concentration time curve (AUC) infinity of QEQ278 [ Time Frame: During first 168 days of treatment ]
  The AUC from time zero to infinity
• Time to reach peak serum concentration (Tmax) of QEQ278 [ Time Frame: During first 168 days of treatment ]
  The time to reach maximum (peak) serum drug concentration after single dose administration
• Elimination half-life (T1/2) of QEQ278 [ Time Frame: During first 168 days of treatment ]
  The elimination half-life associated with the terminal slope of a semi logarithmic concentration-time curve
• Total body clearance (CL) of QEQ278 [ Time Frame: During first 168 days of treatment ]
  The total body clearance of drug from the serum
• Volume of distribution (Vz) of QEQ278 [ Time Frame: During first 168 days of treatment ]
  The apparent volume of distribution during terminal phase
• Incidence of anti-drug antibody (ADA) [ Time Frame: Day 1 and 15 ]
  Immunogenicity of QEQ278

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

Biological: QEQ278

Intravenous dosing of QEQ278

Study Arms

• Experimental: Part 1: Dose escalation
  Dose escalation with QEQ278 single agent
  Intervention: Biological: QEQ278
• Experimental: Part 2: Dose expansion
  Dose expansion with QEQ278 single agent
  Intervention: Biological: QEQ278

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 14, 2022): 125
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 9, 2026
• Estimated Primary Completion Date: January 9, 2026 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Novartis Pharmaceuticals; 1-888-669-6682; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals; +41613241111

• Listed Location Countries: Spain, Belgium, France, Germany, Italy, Japan, Singapore, Taiwan, United States

Administrative Information

• NCT Number: NCT05462873
• Other Study ID Numbers: CQEQ278A12101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Original Responsible Party: Same as current
• Current Study Sponsor: Novartis Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Novartis
• Verification Date: April 2024