A Study to Evaluate the Safety and Preliminary Signs of Efficacy of [177Lu]Lu-OncoFAP-23 Alone or in Combination With L19-IL2 as a Treatment of Metastatic FAP-positive Solid Tumors

NCT06640413 | Recruiting Phase 1 DMC

• 2 other identifiers: PH-FAPLU-02/232023-509453-31-00
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 4

Brief Summary

The aim of this study is to assess the safety of \[177Lu\]Lu-OncoFAP-23 alone or in combination with L19-IL2 for the treatment of advanced/metastatic Fibroblast Activation Protein (FAP)-positive solid tumors and to establish a Recommended Dose (RD).

Conditions

FAP

Keywords

Patients with advanced/metastatic FAP-positive tumors

Outcome Measures

Primary Outcomes (5)

• Dose Limiting Toxicity

  Dose Limiting Toxicity (DLT)

  From Day 1 to 28 of the dose escalation part

• Maximum Tolerated Dose (MTD) and Recommended Dose (RD)

  Maximum Tolerated Dose (MTD) and Recommended Dose (RD)

  From Day 1 to 28 of the dose escalation part

• Maximum Administered Dose (MAD)

  Maximum Administered Dose (MAD)

  From Day 1 to 28 of the dose escalation part

• Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Adverse events (AEs) and Serious Adverse Events (SAEs) assessment based on Common Terminology Criteria for Adverse Events v. 5.0 (CTCAE)

  through study completion, maximum 1 year

• Drug Induced Liver Injury (DILI)

  Drug Induced Liver Injury (DILI) assessment based on Common Terminology Criteria for Adverse Events v. 5.0 (CTCAE)

  through study completion, maximum 1 year

Study Arms (7)

Part I - Dose Escalation - Cohort 1, Arm 1

EXPERIMENTAL

In Arm 1, patients assigned to this cohort 1, receive monotherapy of \[177Lu\]Lu-OncoFAP-23 (3.7 GBq)

Drug: [177Lu]Lu-OncoFAP-23

Part I - Dose Escalation - Cohort 2, Arm 1

EXPERIMENTAL

In Arm 1, patients assigned to this cohort 2, receive monotherapy of \[177Lu\]Lu-OncoFAP-23 (7.4 GBq)

Drug: [177Lu]Lu-OncoFAP-23

Part I - Dose Escalation - Cohort 3, Arm 1

EXPERIMENTAL

In Arm 1, patients assigned to this cohort 3, receive monotherapy of \[177Lu\]Lu-OncoFAP-23 (11.1 GBq)

Drug: [177Lu]Lu-OncoFAP-23

Part I - Dose Escalation - Cohort 4, Arm 2

EXPERIMENTAL

In Arm 2, patients assigned to this cohort 4, receive combination of \[177Lu\]Lu-OncoFAP-23 at at the dose level below the Maximum Tolerated Dose (MTD) with L19IL2 (22.5 Mio IU).

Drug: [177Lu]Lu-OncoFAP-23; Drug: L19IL2

Part I - Dose Escalation - Cohort 5, Arm 2

EXPERIMENTAL

In Arm 2, patients assigned to this cohort 4, receive combination of \[177Lu\]Lu-OncoFAP-23 at MTD with L19IL2 (22.5 Mio IU).

Drug: [177Lu]Lu-OncoFAP-23; Drug: L19IL2

Part II - Dose Expansion - Arm 1

EXPERIMENTAL

10 patients receive the monotherapy of \[177Lu\]Lu-OncoFAP-23 at the recommended dose

Drug: [177Lu]Lu-OncoFAP-23

Part II - Dose Expansion - Arm 2

EXPERIMENTAL

10 patients receive the combination of \[177Lu\]Lu-OncoFAP-23 and L19IL2 at the recommended doses

Drug: [177Lu]Lu-OncoFAP-23; Drug: L19IL2

Interventions

[177Lu]Lu-OncoFAP-23 DRUG

3.7, 7.4, or 11.1 GBq to define the RD

Part I - Dose Escalation - Cohort 1, Arm 1; Part I - Dose Escalation - Cohort 2, Arm 1; Part I - Dose Escalation - Cohort 3, Arm 1; Part I - Dose Escalation - Cohort 4, Arm 2; Part I - Dose Escalation - Cohort 5, Arm 2; Part II - Dose Expansion - Arm 1; Part II - Dose Expansion - Arm 2

L19IL2 DRUG

22.5 Mio IU

Part I - Dose Escalation - Cohort 4, Arm 2; Part I - Dose Escalation - Cohort 5, Arm 2; Part II - Dose Expansion - Arm 2

Eligibility Criteria

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

You may qualify if:

• Patients with advanced/metastatic solid tumors, who have progressed on available standard treatments.
• Patients with FAP-positive tumors as evaluated by \[68Ga\]Ga-OncoFAP-DOTAGA-PET/CT imaging.
• Patients without other therapeutic alternatives with curative or survival prolonging potential as per investigator judgement.
• Male or non-pregnant and non-breast feeding female, age 18 or more.
• Patients must have at least one unidimensionally measurable lesion by computed tomography as defined by RECIST criteria 1.1. This lesion should not have been irradiated during previous treatments.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Survival expectation of more than 12 weeks.
• Ability to undergo standard imaging.
• Documented negative test for Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV). For HBV serology: the determination of HBsAg and anti-HBcAg-Ab is required. In patients with serology documenting previous exposure to HBV (i.e., anti-HBsAg-Ab with no history of vaccination and/or anti-HBcAg-Ab), negative serum HBV-DNA is required. For HCV: HCV-RNA or HCV antibody test. Subjects with a positive test for HCV antibody but no detection of HCV-RNA indicating no current infection are eligible.
• All acute toxic effects (excluding alopecia and fatigue) of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v. 5.0) Grade ≤ 1.
• Female patients: negative blood pregnancy test at Screening for women of childbearing potential (WOCBP)\*. WOCBP must agree to use, from the screening to six months following the last study drug administration, highly effective contraception methods, as defined by the Recommendations for contraception and pregnancy testing in clinical ; issued by the Head of Medicine Agencies; Clinical Trial Facilitation Group (www.hma.eu/ctfg.html) and which include, for instance, progesterone-only or combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion or vasectomized partner.
• Male patients: male subjects able to father children must agree to use two acceptable methods of contraception throughout the study (e.g., condom with spermicidal gel). Double-barrier contraception is required.
• A personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study and has given consent to participate in the study.
• Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
• Women of childbearing potential are defined as females who have experienced menarche, are not postmenopausal (12 months with no menses without an alternative medical cause) and are not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy or bilateral salpingectomy).

You may not qualify if:

• Any cancer therapy within 4 weeks of study entry.
• Active or history of autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent.
• Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, Iodine-131, Lutetium-177 conjugates or hemi-body irradiation within 6 months prior to enrollment.
• White blood cell count (WBC) minor than 2.5 x 109/L, absolute neutrophil count (ANC) minor than 1.5 x 109/L, platelets minor than 100 x 109/L or hemoglobin (Hb) minor than 9.0 g/dl,
• Chronically impaired renal function as expressed by creatinine clearance minor than 60 mL/min or serum creatinine major than 1.5 ULN.
• Inadequate liver function (Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) ≥ 3 x Upper Limit of Normal (ULN), or Alkaline Phosphatase (ALP) or Gamma Glutamyl Transferase (GGT) ≥ 2.5 x ULN, or total bilirubin ≥ 1.5 x ULN). For patients with metastatic lesions in the liver ALT, AST, GGT or ALP ≥ 5 x ULN.
• Presence of cirrhosis or active hepatitis.
• Patients with Central Nervous System (CNS) metastases.
• History within the last year of cerebrovascular disease and/or acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
• Heart insufficiency (major Grade II, New York Heart Association (NYHA) criteria).
• Clinically significant cardiac arrhythmias or requiring permanent medication.
• Abnormal Left Ventricular Ejection Fraction (LVEF) or any other abnormalities observed during baseline Electrocardiogram (ECG) and echocardiogram investigations that are considered as clinically significant by the investigator. Subjects with current, or a history of QT/QTc prolongation would be excluded. In particular: - patients with a marked prolongation of QT/QTc interval (e.g., repeated demonstration of QTc major than 480 milliseconds using Fredricia's QT correction formula) are excluded; - patients with a history of risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of prolonged QT syndrome) are excluded; - patients who require the use of concomitant medications that prolong the QT/QTc interval are excluded.
• Cardioversion in the previous 12 months
• Uncontrolled hypertension as defined by systolic blood pressure ≥ 140 mmHg and diastolic blood pressure ≥ 90 mmHg at 3 consecutive measurements performed within one week. Note: if the first blood pressure measurement is below threshold for systolic or diastolic blood pressure, it is not required to repeat the measurement.
• Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine classification).

Sponsors & Collaborators

• Philogen S.p.A.: lead

Study Sites (4)

ASST Papa Giovanni XXIII Piazza OMS

Bergamo, Bergamo, 24127, Italy

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Milano, 20133, Italy

RECRUITING

Istituto Europeo di Oncologia

Milan, Milano, 20141, Italy

NOT YET RECRUITING

Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" Via Mariano Semmola

Naples, Napoli, 80131, Italy

NOT YET RECRUITING

Central Study Contacts

Jacqueline Mock, PhD

CONTACT

+41435448802; regulatory@philogen.com

Federica Bastioli, Pharmaceutical Chemist

CONTACT

regulatory@philogen.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In Part I patients are assigned to 5 sequential dose escalation cohorts. In this part, two arms are foreseen: Arm 1 foresees cohort 1-3 with monotherapy of \[177Lu\]Lu-OncoFAP-23 (3.7, 7.4, 11.1 GBq respectively); Arm 2, only opened when the MTD and RD is established, has cohorts 4-5 that are run with \[177Lu\]Lu-OncoFAP-23 in combination with L19IL2 at 22.5 Mio International Units (IU). In Part II, 10 patients are randomly assigned to Arm 1 (monotherapy of \[177Lu\]Lu-OncoFAP-23 at the recommended dose) and 10 patients are randomly assigned to Arm 2 (combination of \[177Lu\]Lu-OncoFAP-23 and L19IL2 at the recommended doses).

Study Record Dates

• First Submitted: October 10, 2024
• First Posted: October 15, 2024
• Study Start: October 31, 2025
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (4)