FIH XON7 in Advanced/Metastatic Solid Tumors

NCT06154291 | Recruiting Phase 1 DMC

• 2 other identifiers: XT 23-012023-505266-29-00
• Study Type: interventional
• Target: 255
• Locations: 2 countries
• Sites: 5

Brief Summary

This is a two-stage trial consisting of a Part I, dose escalation and dose-finding component to establish the Maximal Tolerated Dose (MTD), if any, and Recommended Part 2 Dose (RP2D) of XON7, followed by a Part II component to investigate anti-tumors efficacy in selected solid tumor types and to further evaluate safety and tolerability of XON7 at RP2D.

Conditions

Advanced Solid Tumor; Metastatic Cancer

Keywords

Advanced or metastatic solid tumors

Outcome Measures

Primary Outcomes (42)

• Dose Escalation part: Dose Limiting Toxicities (DLTs)

  Investigator defined DLT during first treatment cycle

  At the end of Cycle 1 (28 days)

• Dose Escalation part: treatment emergent adverse events (TEAEs)

  An overall summary of AE occurrences with onset during the first treatment cycle will be presented; this will include the following AE attributes: * Preferred term, * Maximum CTCAE grade, * Outcome, * Time to first occurrence \[days\].

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Leucocytes count

  Incidence and magnitude of clinically significant changes in Leucocytes Count (G/L)

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Red Blood Cells Count

  Incidence and magnitude of clinically significant changes in Red Blood Cells Count (T/L)

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Hemoglobin

  Incidence and magnitude of clinically significant changes in Hemoglobin (g/dL).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Hematocrit

  Incidence and magnitude of clinically significant changes in Hematocrit (%).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Absolute Neutrophil Count

  Incidence and magnitude of clinically significant changes in Absolute Neutrophil Count (G/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Absolute Eosinophil Count

  Incidence and magnitude of clinically significant changes in Absolute Eosinophil Count (G/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Absolute Basophil Count

  Incidence and magnitude of clinically significant changes in Absolute Basophil Count (G/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Absolute Lymphocytes Count

  Incidence and magnitude of clinically significant changes in Absolute Lymphocytes Count (G/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Absolute Monocytes Count

  Incidence and magnitude of clinically significant changes in Absolute Monocytes Count (G/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Platelet Count

  Incidence and magnitude of clinically significant changes in Platelet Count (G/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Albumin

  Incidence and magnitude of clinically significant changes in Albumin (g/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Bicarbonate

  Incidence and magnitude of clinically significant changes in Bicarbonate (mmol/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Total Bilirubin

  Incidence and magnitude of clinically significant changes in Total Bilirubin (µmol/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Calcium

  Incidence and magnitude of clinically significant changes in Calcium (mmol/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Urea

  Incidence and magnitude of clinically significant changes in Urea (mmol/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Chloride

  Incidence and magnitude of clinically significant changes in Chloride (mmol/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Creatinine

  Incidence and magnitude of clinically significant changes in Creatinine (µmol/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Creatinine Clearance

  Incidence and magnitude of clinically significant changes in Creatinine Clearance (mL/min).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Glucose

  Incidence and magnitude of clinically significant changes in Glucose (mmol/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Magnesium

  Incidence and magnitude of clinically significant changes in Magnesium (mmol/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Phosphate

  Incidence and magnitude of clinically significant changes in Phosphate (mmol/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Potassium

  Incidence and magnitude of clinically significant changes in Potassium (mmol/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Sodium

  Incidence and magnitude of clinically significant changes in Sodium (mmol/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Total Protein

  Incidence and magnitude of clinically significant changes in Total Protein (g/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Alanine aminotransferase (ALT)

  Incidence and magnitude of clinically significant changes in Alanine aminotransferase (ALT) (U/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Aspartate aminotransferase (AST)

  Incidence and magnitude of clinically significant changes in Aspartate aminotransferase (AST) (U/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Gamma-glutamyl transférase (GGT)

  Incidence and magnitude of clinically significant changes in Gamma-glutamyl transférase (GGT) (U/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Alkaline Phosphatase (ALP)

  Incidence and magnitude of clinically significant changes in Alkaline Phosphatase (ALP) (U/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Lactate dehydrogenase (LDH)

  Incidence and magnitude of clinically significant changes in Lactate dehydrogenase (LDH) (U/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Amylase

  Incidence and magnitude of clinically significant changes in Amylase (U/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Lipase

  Incidence and magnitude of clinically significant changes in Lipase (U/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Total Protein Creatine Kinase (CK)

  Incidence and magnitude of clinically significant changes in Total Protein Creatine Kinase (CK) (U/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Creatine kinase - cardiac muscle isoenzyme (CK-MB)

  Incidence and magnitude of clinically significant changes in Creatine kinase - cardiac muscle isoenzyme (CK-MB) (U/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Troponin T

  Incidence and magnitude of clinically significant changes in Troponin T (ng/L).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Prothrombin Time (PT)

  Incidence and magnitude of clinically significant changes in Prothrombin Time (PT) (Sec).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in INR (if under VKA Therapy)

  Incidence and magnitude of clinically significant changes in INR (if under VKA Therapy)

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant changes in Activated Partial Thromboplastin Time (aPTT)

  Incidence and magnitude of clinically significant changes in Activated Partial Thromboplastin Time (aPTT) (Sec).

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant findings in blood pressure (BP)

  Incidence and severity of clinically significant findings in blood pressure: Significant blood pressure increase will be defined as BP \>150/100 mmHg in a subject without a history of hypertension or increased \>20 mmHg (diastolic) from baseline measurement in a subject with a previous history of hypertension.

  At the end of Cycle 1 (28 days)

• Dose Escalation part: clinically significant findings in electrocardiogram (ECGs)

  Incidence of clinically significant findings in Electrocardiogram (ECG): Significant QTc prolongation will be defined as an interval ≥500 msec or an interval which increases by ≥60 msec over baseline

  At the end of Cycle 1 (28 days)

• Expansion part: Anti-tumors efficacy

  Objective response rate (ORR): defined as the proportion of participants with a confirmed complete response \[CR\] or confirmed partial response \[PR\] assessed by investigators according to RECIST v1.1.

  Within 3 months after XON7 initiation

Secondary Outcomes (65)

• Pharmacokinetics (PK) of XON7 (Part 1): Cmax

  Cycle 1-Day 1 Predose and Postdose: 5 minutes; 1; 2; 4; 8; 24; 72 or 96; 144 hours after the end of infusion. Cycle 1 Day 15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 7 Day 1: Predose and 5 minutes after the end of infusion

• Pharmacokinetics (PK) of XON7 (Part 2): Cmax

  Cycle 1-Day 1; Cycle 2-Day 1; Cycle 3-Day 1; Cycle 6-Day 1; Cycle 9-Day1 and Cycle 12-Day 1: Predose and 5 minutes after the end of infusion

• Pharmacokinetics (PK) of XON7 (Part 1): Tmax

  Cycle 1-Day 1 Predose and Postdose: 5 minutes; 1; 2; 4; 8; 24; 72 or 96; 144 hours after the end of infusion. Cycle 1 Day 15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 7 Day 1: Predose and 5 minutes after the end of infusion

• Pharmacokinetics (PK) of XON7 (Part 2): Tmax

  Cycle 1-Day 1; Cycle 2-Day 1; Cycle 3-Day 1; Cycle 6-Day 1; Cycle 9-Day1 and Cycle 12-Day 1: Predose and 5 minutes after the end of infusion

• Pharmacokinetics (PK) of XON7 (Part 1): AUC

  Cycle 1-Day 1 Predose and Postdose: 5 minutes; 1; 2; 4; 8; 24; 72 or 96; 144 hours after the end of infusion. Cycle 1 Day 15; Cycle 2 Day 1; Cycle 3 Day 1; Cycle 7 Day 1: Predose and 5 minutes after the end of infusion

Study Arms (1)

Dose Escalation part then Expansion part

EXPERIMENTAL

Dose Escalation part: Six dose levels are planned: 1.5; 3; 6; 12; 16 and 20mg/kg Expansion part: Up to 7 cohorts (1 cohort for one selected solid tumor type) could be investigated: Cohort E1: Non-small cell lung cancer (NSCLC) Cohort E2: Gastro-esophageal adenocarcinoma Cohort E3: Colorectal cancer (CRC) Cohort E4: Pancreatic cancer Cohort E5: Sarcoma Cohort E6: Triple-negative breast cancer (TNBC) Cohort E7: Ovarian cancer

Drug: XON7

Interventions

XON7 DRUG

The trial intervention (XON7) is a glyco-humanized polyclonal antibody drug which is formulated for intravenous (IV) administration

Dose Escalation part then Expansion part

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide signed, written informed consent.
• Male and female participant, age ≥ 18 years old (at the time consent is obtained)
• Solid tumors indications:
• Participant in phase I, must have a histologically or cytologically confirmed advanced or metastatic solid tumors for which no effective standard therapy is available. All tumor types except glioblastoma, could be included.
• Participant in phase II, must have histologically or cytologically confirmed advanced or metastatic solid tumors of the following: NSCLC, gastro-esophageal adenocarcinoma, CRC, pancreatic cancer, Sarcoma, TNBC, or ovarian cancer.
• Line of treatment: Participant must have solid tumors progressing after ≤ 4 lines of standard appropriate anticancer therapies for the specific tumor type, or for which the patient is ineligible. Participants whose cancers harbor molecular alterations for which targeted therapy is standard of care should have received health authority-approved appropriate targeted therapy for their tumor types before enrollment.
• Measurable disease per RECIST version 1.1 - v5
• (ECOG) performance status (PS) 0-1
• Life expectancy of at least 12 weeks.
• Adequate organ function
• QT duration corrected for heart rate by Fridericia's formula (QTcF) \<450 msec or QTcF \<480 msec for participants with bundle branch block.
• Female participant who are not of child-bearing potential, and female participants of child-bearing potential who have a negative serum pregnancy test within 7 days prior to initial trial treatment. Female participants of child-bearing potential, and all male partners must consent to use a medically acceptable method of contraception throughout the trial period and for at least 60 days after the last dose of XON7. A barrier method of contraception must be included.
• Male participant willing to use adequate contraceptive measures throughout the trial period and for at least 60 days after the last dose of trial intervention.
• For phase II, participant in pharmacodynamics cohort must provide biopsy of a tumor lesion not previously irradiated during the screening period and must agree to provide at least one additional on-treatment biopsy between day 36 and 42 after trial intervention administration.
• For phase II, participant in pharmacodynamics cohort must have accessible tumor tissue available for fresh biopsy except for ovarian cancer and sarcoma.

You may not qualify if:

• A participant who has received more than 4 prior lines of therapy for advanced or metastatic disease.
• A participant who has had a prior anti-cancer mAb within 3 weeks prior to trial Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier prior to trial Day 1.
• A participant who has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to trial Day 1 or who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent (Except alopecia, hearing loss, grade 2 neuropathy or endocrinopathy managed with replacement therapy).
• A participant with ≥Grade 3 toxicity related to prior immunotherapy leading to treatment discontinuation.
• A participant whose toxicity related to prior treatment has not resolved to Grade 1 (except alopecia, hearing loss, grade 2 neuropathy or endocrinopathy managed with replacement therapy).
• A participant who has received major surgery 2 weeks before the first dose of trial treatment or has not recovered adequately from the toxicity and/or complications from any surgery (major or minor) before initiating trial treatment.
• Concomitant use of another experimental drug, or wash-out period of at least 5 half-lives for a previous experimental drug not completed before start of trial intervention
• Participant treated with drugs known to prolong the QT interval
• Participant with carcinomatous meningitis.
• Central nervous system (CNS) metastases, with the exception of individuals who have been previously treated CNS metastases, are asymptomatic, and have had no requirement for steroids for 3 weeks prior to first dose of trial drug.
• Malignancies other than disease under trial within 3 years prior to first dose of trial intervention.
• History of autoimmune disease
• Active or uncontrolled infections requiring systemic treatment (known human immunodeficiency virus infection, or positive test for hepatitis B surface antigen or hepatitis C).
• Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the trial such as history or evidence of cardiovascular risk including any of the following:
• Recent (within the past 6 months) history of serious uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities including second degree (Type II) or third-degree atrioventricular block.

Sponsors & Collaborators

• Xenothera SAS: lead

Study Sites (5)

Institut Jules Bordet

Anderlecht, 1070, Belgium

RECRUITING

Institut Bergonié

Bordeaux, 33076, France

RECRUITING

Centre Léon Bérard

Lyon, 69003, France

RECRUITING

Hôpital Foch

Suresnes, 92150, France

RECRUITING

IUCT-Oncopole

Toulouse, 31100, France

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jaafar BENNOUNA, MD

  Hôpital Foch

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Françoise SHNEIKER, MD

CONTACT

+33652720301; francoise.shneiker@xenothera.com

Alain BALEYDIER

CONTACT

+33672800375; alain.baleydier@xenothera.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The Part I component is a multicenter, open-label, multiple-dose, dose escalation, first-in-human study. Six dose levels are planned: 1.5; 3; 6; 12; 16 and 20mg/kg, Q2W (once every two weeks). Up to 45 participants with relapsed or refractory, advanced or metastatic solid tumors will be included. The Part II component is a multi-center, open-label, non-randomized, multi-cohorts, expansion trial with adaptive design. The selected cohorts of the study will investigate RP2D to determine the anti-tumors efficacy, safety, and tolerability of XON7 in participants with relapsed or refractory, advanced or metastatic solid tumors after failure to standard of care treatments. Up to 7 cohorts could be investigated. A maximum of 30 participants will be enrolled in each cohort.

Study Record Dates

• First Submitted: November 6, 2023
• First Posted: December 4, 2023
• Study Start: November 14, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): November 1, 2027
• Last Updated: June 22, 2025

Record last verified: 2025-06

Locations

FR (4); BE (1)