FIH XON7 in Advanced/Metastatic Solid Tumors | NCT06154291

ID	Type	Description	Link
2023-505266-29-00	Other Identifier	EU CT number

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Secondary Outcomes

Measure	Description	Time Frame
Pharmacokinetics (PK) of XON7 (Part 1): Cmax	XON7 peak plasma concentration (Cmax) in plasma	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

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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.
In France, a participant will be eligible for inclusion in this trial only if either affiliated to or a beneficiary of a social security category.
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.

Exclusion Criteria:

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.
- Documented cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting, or bypass grafting within the past 6 months before enrollment.
- Documented congestive heart failure (Class II, III, or IV) as defined by the New York Heart Association functional classification system (NYHA, 1994).
Prior allogeneic or autologous bone marrow transplantation or other solid organ transplantation.
Current active liver or biliary disease (Except for Gilbert's syndrome or asymptomatic gallstones, liver metastases, or otherwise stable chronic liver disease per investigator assessment).
Concurrent medical condition requiring the use of systemic immunosuppressive medications within 28 days before the first dose of trial treatment.
Recent history (within the past 6 months) of acute diverticulitis, inflammatory bowel disease, intra-abdominal abscess, or gastrointestinal obstruction.
Current or history of idiopathic pulmonary fibrosis, interstitial lung disease, or organizing pneumonia. Note: post-radiation changes in the lung related to prior radiotherapy and/or asymptomatic radiation-induced pneumonitis not requiring treatment may be permitted if agreed by the investigator and Medical Monitor.
History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
Recent history (within 6 months) of uncontrolled symptomatic ascites or pleural effusions.
Participant who has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony- stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM- CSF], recombinant erythropoietin) within 2 weeks before the first dose of trial intervention.
Known, current drug or alcohol abuse.
Female participant who is pregnant or lactating.
Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
Inability or unwillingness to comply with trial and/or follow-up procedures outlined in the protocol.
For France, patients under legal protection (safeguard, guardianship, curatorship)

Name	Role	Phone	Extension	Email
Françoise SHNEIKER, MD	Contact	+33652720301		francoise.shneiker@xenothera.com
Alain BALEYDIER	Contact	+33672800375		alain.baleydier@xenothera.com

ID	Term
D009385	Neoplastic Processes
D009369	Neoplasms
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms