Trial Title:
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
NCT ID:
NCT06640413
Condition:
FAP
Conditions: Keywords:
Patients with advanced/metastatic FAP-positive tumors
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
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).
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
[177Lu]Lu-OncoFAP-23
Description:
3.7, 7.4, or 11.1 GBq to define the RD
Arm group label:
Part I - Dose Escalation - Cohort 1, Arm 1
Arm group label:
Part I - Dose Escalation - Cohort 2, Arm 1
Arm group label:
Part I - Dose Escalation - Cohort 3, Arm 1
Arm group label:
Part I - Dose Escalation - Cohort 4, Arm 2
Arm group label:
Part I - Dose Escalation - Cohort 5, Arm 2
Arm group label:
Part II - Dose Expansion - Arm 1
Arm group label:
Part II - Dose Expansion - Arm 2
Intervention type:
Drug
Intervention name:
L19IL2
Description:
22.5 Mio IU
Arm group label:
Part I - Dose Escalation - Cohort 4, Arm 2
Arm group label:
Part I - Dose Escalation - Cohort 5, Arm 2
Arm group label:
Part II - Dose Expansion - Arm 2
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).
Detailed description:
This study is a prospective phase I, open-label, multiple ascending, multi-center dose
escalation study to evaluate the safety and preliminary signs of efficacy of
[177Lu]Lu-OncoFAP-23 alone and in combination with the antibody-cytokine conjugate
L19-IL2 for the treatment of advanced/metastatic FAP-positive solid tumors.
Eligible patients for this trial are male or non-pregnant and non-breastfeeding females
aged 18 years or more, able to give informed consent.
Up to 56 evaluable patients will be enrolled in the trial and the trial is divided into
two parts:
1. Part I - Dose escalation part (2-36 pts) This dose escalation part of the study is
designed as a standard 3+3 escalation scheme. Not more than 2 patients per cohort
are treated simultaneously during the Dose Limiting Toxicity (DLT) observation
period from Day 1 to Day 28 of the first cycle. Patients per cohort will be assigned
to different dose levels of the study drug.
2. Part II - Dose expansion part (20 pts) After completion of the dose escalation part,
additional 20 patients will be enrolled at the RD to better understand the safety
profile and to explore early signs of efficacy in different disease indications.
Patients will be randomly assigned to arm 1 (monotherapy) or arm 2 (combination
therapy) (10 patients each).
Both in part I and II, patients can receive up to 4 consecutive cycles of radioligand
therapy every 8 (± 1) weeks.
The primary objective 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 FAP-positive
malignancies and to establish a Recommended Dose (RD).
Secondary objectives include evaluation of pharmacokinetics and the collection of initial
signs of efficacy of the treatment.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients with advanced/metastatic solid tumors, who have progressed on available
standard treatments.
2. Patients with FAP-positive tumors as evaluated by [68Ga]Ga-OncoFAP-DOTAGA-PET/CT
imaging.
3. Patients without other therapeutic alternatives with curative or survival prolonging
potential as per investigator judgement.
4. Male or non-pregnant and non-breast feeding female, age 18 or more.
5. 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.
6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
7. Survival expectation of more than 12 weeks.
8. Ability to undergo standard imaging.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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).
Exclusion Criteria:
1. Any cancer therapy within 4 weeks of study entry.
2. Active or history of autoimmune disease that might deteriorate when receiving an
immuno-stimulatory agent.
3. 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.
4. 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,
5. Chronically impaired renal function as expressed by creatinine clearance minor than
60 mL/min or serum creatinine major than 1.5 ULN.
6. 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.
7. Presence of cirrhosis or active hepatitis.
8. Patients with Central Nervous System (CNS) metastases.
9. History within the last year of cerebrovascular disease and/or acute or subacute
coronary syndromes including myocardial infarction, unstable or severe stable angina
pectoris.
10. Heart insufficiency (major Grade II, New York Heart Association (NYHA) criteria).
11. Clinically significant cardiac arrhythmias or requiring permanent medication.
12. 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.
13. Cardioversion in the previous 12 months
14. 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.
15. Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine
classification).
16. Severe diabetic retinopathy such as severe non-proliferative retinopathy and
proliferative retinopathy.
17. Pregnancy or lactation or unwillingness to use adequate method of birth control.
18. Any severe concomitant condition which in the opinion of investigators makes it
undesirable for the patient to participate in the study or which could jeopardize
compliance with the protocol.
19. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery)
within 4 weeks of administration of the study drug.
20. Serious, non-healing wound, ulcer or bone fracture.
21. Known history of allergy to an excipient in study medication or any other
intravenously administered human proteins/peptides/antibodies
22. Systemic chronic steroid therapy (major than 10 mg/day prednisone or equivalent) or
any other immunosuppressive therapy within 14 days prior to study treatment start.
Topical, inhaled, nasal and ophthalmic steroids are allowed.
23. Presence of active and uncontrolled infections or other severe concurrent disease,
which, in the opinion of the investigator, would place the patient at undue risk or
interfere with the study.
24. Concurrent or previous malignancies (other than the indication for this trial),
unless a complete remission without further recurrence was achieved at least 2 years
prior to study treatment start.
25. Growth factors or immunomodulatory agents within 7 days prior to study treatment
start.
26. Deep vein thrombosis, pulmonary embolism, or other acute vascular events within 6
months.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
ASST Papa Giovanni XXIII Piazza OMS
Address:
City:
Bergamo
Zip:
24127
Country:
Italy
Contact:
Last name:
Paola Anna Erba, Prof MD PhD
Phone:
+390352674642
Email:
paolaanna.erba@unimib.it
Contact backup:
Last name:
Paola Anna Erba, Prof MD PhD
Facility:
Name:
Fondazione IRCCS Istituto Nazionale dei Tumori
Address:
City:
Milano
Zip:
20133
Country:
Italy
Contact:
Last name:
Margarita Kirienko, MD PhD
Phone:
+390223903084
Email:
margarita.kirienko@istitutotumori.mi.it
Contact backup:
Last name:
Margarita Kirienko, MD PhD
Facility:
Name:
Istituto Europeo di Oncologia
Address:
City:
Milano
Zip:
20141
Country:
Italy
Contact:
Last name:
Giuseppe Curigliano, MD PhD
Phone:
+390257489960
Email:
Giuseppe.curigliano@ieo.it
Contact backup:
Last name:
Giuseppe Curigliano, MD PhD
Facility:
Name:
Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" Via Mariano Semmola
Address:
City:
Napoli
Zip:
80131
Country:
Italy
Contact:
Last name:
Secondo Lastoria, MD
Phone:
+3908117770544
Email:
s.lastoria@istitutotumori.na.it
Contact backup:
Last name:
Secondo Lastoria, MD
Start date:
December 31, 2024
Completion date:
December 31, 2028
Lead sponsor:
Agency:
Philogen S.p.A.
Agency class:
Industry
Source:
Philogen S.p.A.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06640413
