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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

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

XON7

Françoise SHNEIKER, MD

Alain BALEYDIER

Ahmad Hussein AWADA, MD

Jean-Yves BLAI, MD

Jaafar BENNOUNA, MD

Jean-Pierre DELORD, MD

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.

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.

FIH XON7 in Advanced/Metastatic Solid Tumors

Phase I/II, Multi Center, Open Label, First-in-human, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics, and Anti-tumors Efficacy of the Glyco-humanized Polyclonal Antibody XON7 in Patients With Advanced or Metastatic Solid Tumors

Investigator defined DLT during first treatment cycle

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 \[days\].

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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

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.

XON7 peak plasma concentration (Cmax) in plasma

Time to peak drug concentration in plasma (Tmax)

Area under the plasma concentration versus time curve (AUC). AUC24hours; AUC0-14days and AUC15-28days will be assessed

Trough concentration (Ctrough) is the concentration reached by XON7 immediately before the next dose is administered

Cmin for the minimum blood plasma concentration reached by XON7 during the time interval between administration of two doses

Half-life (T1/2) refers to the time required for plasma concentration of XON7 to decrease by 50%

Clearance (CL) is the volume of blood or plasma cleared of XON7 from the body per unit of time

Volume of distribution (Vd) is defined as the total amount of XON7 in the body divided by its concentration in plasma

Number of participants who develop detectable anti-drug antibodies

Percentage of participants who develop detectable anti-drug antibodies

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

Clinical Benefit Rate (CBR) defined as the proportion of participants who achieve CR, PR, and durable SD \[SD≥24 weeks\] assessed by investigators according to the RECIST criteria v 1.1.

Disease control rate (DCR): defined as the proportion of participants who achieve confirmed complete response \[CR\], confirmed partial response \[PR\] or stable disease \[SD\] assessed by investigators according to the RECIST criteria version 1.1.

Duration of response (DoR): defined as the time interval between the first confirmed objective response (CR or PR per RECIST 1.1 by investigators) and the first occurrence of objective tumor progression (Progressive disease (PD) per RECIST 1.1 by investigators) or death from any cause.

Time to response (TTR): defined as the time from the date of XON7 initiation to first confirmed objective response (CR or PR per RECIST 1.1 by investigators)..

Progression-free survival (PFS): defined as the time from the date of XON7 initiation to the date of first documented progression (RECIST 1.1 by investigators) or death.

Overall survival (OS): defined as the time interval between the date of XON7 initiation and the date of death due to any cause.

Spots Global Cancer Trial Database for FIH XON7 in Advanced/Metastatic Solid Tumors

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