A Phase I Study to Evaluate the Safety and Efficacy of L19IL2 in Combination With Ruxolitinib in Patients With Advanced Solid Tumors

This trial aims to address unmet medical needs in advanced solid tumors, specifically metastatic clear cell renal carcinoma, locally advanced or metastatic pancreatic adenocarcinoma, and metastatic colorectal adenocarcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma Metastatic; Renal Carcinoma Metastatic; Metastatic Colorectal Carcinoma (mCRC)
• Intervention / Treatment: Drug: L19IL2; Drug: Ruxolitinib

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Claudio Nanni; Phone Number: +39 057717816; Email: regulatory@philogen.com
• Study Contact Backup: Name: Federica Bastioli; Phone Number: +39 057717816; Email: regulatory@philogen.com

Study Locations

• Italy
  • Roma
    • Roma, Roma, Italy, 00168
      • Fondazione Policlinico Gemelli Unità di Fase 1: Unità di Farmacologia Clinica
      • Contact: Gennaro Daniele; Phone Number: +39 06 30158802; Email: gennaro.daniele@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of one of the following tumor types for which no further approved systemic treatment options are available:

   1. Unresectable locally advanced or metastatic pancreatic ductal adenocarcinoma, that has progressed following:

      • at least one prior line containing FOLFIRINOX and/or gemcitabine plus nab-paclitaxel, and
      • at least one approved second-line regimen (e.g., 5-FU/leucovorin plus liposomal irinotecan), or where these regimens are not suitable due to contraindication or prior intolerance

   2. Metastatic proficient mismatch repair / microsatellite stable (pMMR/MSS), BRAF V600E-negative colorectal adenocarcinoma, that has progressed following:

      • at least one prior line of systemic therapy including a fluoropyrimidine and oxaliplatin or irinotecan, with or without anti-VEGF and, if RAS wild-type, with or without anti-EGFR, and
      • at least one approved subsequent line of therapy with trifluridine-tipiracil, regorafenib or fruquintinib, or where these agents are not suitable due to contraindication or prior intolerance;

   3. Metastatic clear cell renal cell carcinoma, that has progressed following:

      • at least one prior PD-(L)1-based systemic regimen, and
      • at least one VEGF-targeted tyrosine kinase inhibitor (TKI), or where these treatments are not suitable due to contraindication or prior intolerance
2. Patients must have no further approved and available therapy options or be documented as ineligible or intolerant.
3. Patients must have radiographic disease progression on/after the last line of prior treatment.
4. At least one unidimensionally measurable lesion as defined by RECIST v.1.1.
5. Eastern cooperative oncology group (ECOG) performance status ≤ 2.
6. Patient has an estimated life expectancy of at least 12 weeks.
7. Hemoglobin > 10.0 g/dL.
8. Platelets ≥ 100 x 109/L.
9. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
10. Negative TB test (e.g., Mantoux or Quantiferon assay).
11. Documented negative test for HIV, HBV, HCV excluding active infection is needed. 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-HBs Ab with no history of vaccination and/or anti-HBc 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.
12. Serum creatinine < 1.5 x ULN and estimated Glomerular Filtration Rate (eGFR) value above 75 mL/min/1.73m2. An age-calibrated definition of Chronic Kidney Disease (CKD) has been proposed to distinguish age-related from disease-related changes in eGFR. For patients younger than 40 years, CKD is defined by estimated Glomerular Filtration Rate (eGFR) below 75 mL/min/1.73m2.
13. All acute toxic effects (excluding alopecia) of any prior therapy must have been resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v.5.0) Grade ≤ 1.
14. Women Of Childbearing Potential (WOCBP) must have negative pregnancy test results at screening. WOCBP must be using, from screening to six months following the last study treatment administration, highly effective contraception methods, as defined by the "Recommendations for contraception and pregnancy testing in clinical trials" issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group 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, vasectomized partner. Double-barrier contraception is required.
15. Male patients with WOCBP partners must agree to use simultaneously two acceptable methods of contraception (i.e. spermicidal gel plus condom) from the screening to six months following the last study treatment administration. Double-barrier contraception is required.
16. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria:

1. Patients with primary brain tumors, brain metastases or CNS disease will be excluded.
2. Chemotherapy, immunotherapy, or radiation therapy at the tumor sites within 4 weeks prior to study treatment start.
3. Active or history of autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
4. Previous or concurrent cancer type that is distinct from the cancer being evaluated in this study. Exception made for any other cancer curatively treated ≥ 2 years prior to study treatment start.
5. Presence of active severe bacterial or viral 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.

6. Impaired cardiocirculatory functions due to any of the following conditions:

   a History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.

   b Inadequately controlled cardiac arrhythmias including atrial fibrillation. c Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria). d Any abnormalities observed during baseline ECG and Echocardiogram investigations are considered clinically significant by the investigator.

   e Uncontrolled hypertension defined by systolic blood pressure ≥ 140 mmHg and diastolic blood pressure ≥ 90 mmHg.

   f Ischemic peripheral vascular disease (Grade IIb-IV).

7. Known arterial aneurysms.
8. INR > 3.
9. Inadequate liver function (ALT, AST, ALP ≥ 2.5 x ULN or total bilirubin ≥ 2.0 x ULN). At the discretion of the investigator, an increased exclusion threshold for patients with liver metastasis can be accepted as follows: ALT, AST and ALP ≥ 5 x ULN.
10. Known uncontrolled coagulopathy or bleeding disorder, if the subject is being treated for coagulopathy or bleeding disorder and has tests within screening limits, he/she may be included.
11. Known hepatic cirrhosis or severe pre-existing hepatic impairment (Child-Pugh class B or C).
12. Moderate to severe respiratory failure.
13. Patient requires or is taking systemic corticosteroids (> 10 mg/day prednisone or equivalent) or other immunosuppressant drugs on a long-term basis. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions and asthma/COPD is not considered an exclusion criterion.
14. Known history of allergy to an excipient in study medication (e.g. IL2, ruxolitinib) or other human proteins/peptides/antibodies.
15. Pregnancy or breast-feeding.
16. Severe diabetic retinopathy.
17. Recovery from major trauma including surgery within 4 weeks prior to enrollment.
18. Patient with iatrogenic or pathologic severe immune suppression.
19. Requirement of concurrent use of other anti-cancer treatments or agents other than study medication.
20. Patient taking herbal medications within 7 days prior to study treatment start.
21. Anticoagulation therapy with P2Y12 antagonists (e.g., clopidogrel, ticagrelor) and vitamin K antagonists (e.g., phenprocoumon, warfarin).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental L19IL2 dose escalation intravenous administration	Drug: L19IL2; Intravenous administration
Experimental: Experimental L19IL2 + Ruxolitinib dose escalation intravenous administration	Drug: L19IL2; Intravenous administration; Drug: Ruxolitinib; 10 mg twice, oral administration
Experimental: Experimental L19IL2 + Ruxolitinib dose expansion intravenous administration	Drug: L19IL2; Intravenous administration; Drug: Ruxolitinib; 10 mg twice, oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
STEP A and STEP B: DLT	Occurrence of Dose Limiting Toxicity (DLT) of L19IL2 alone and in combination with ruxolitinib	From Day 1 to Day 28 of the treatment
Safety (AE)	Adverse Events (AEs) of administration of L19IL2 alone and in combination with ruxolitinib, assessed by Common Toxicity Criteria (version 5.0, CTCAE)	Through study completion, an average of 1 year
Safety (SAEs)	Serious Adverse Events(SAEs) of administration of L19IL2 alone and in combination with ruxolitinib, assessed by Common Toxicity Criteria (version 5.0, CTCAE)	Through study completion, an average of 1 year
Safety (DILI)	Evaluation of possible Drug Induce Liver Injury (DILI), caused by L19IL2 alone and in combination with ruxolitinib, assessed by Common Toxicity Criteria (version 5.0, CTCAE)	Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	Overall Response Rate (ORR, including CR and PR) as per RECIST 1.1	Every 8 weeks from treatment start (every 2 cycles; each cycle is 28 days)
Disease Control Rate (DCR)	Disease Control Rate (DCR, including CR, PR, and SD) as per RECIST 1.1	Every 8 weeks from treatment start (every 2 cycles; each cycle is 28 days)
DoR	Duration of Response (DoR)	Every 8 weeks from treatment start (every 2 cycles; each cycle is 28 days)
PSF	Progression Free Survival (PFS)	Every 8 weeks from treatment start (every 2 cycles; each cycle is 28 days)
Human anti-fusion protein antibody (HAFA)	Blood samples will be obtained to assess the potential development of antibody to L19IL2.	Day 1 and 8 of cycle 1; Day 1 of cycle 2, 3, 4, 5, 6. Each cycle is 28 days.
Maximum Plasma Concentration (Cmax)	Maximum observed plasma concentration (Cmax) of L19IL2 and ruxolitinib following administration	Day 1, 2, 8, 15, 22, 23 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 5, and 6 (each cycle is 28 days)
Time to Maximum Plasma Concentration (Tmax)	Time to reach maximum observed plasma concentration (Tmax) of L19IL2 and ruxolitinib.	Day 1, 2, 8, 15, 22, 23 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 5, and 6 (each cycle is 28 days)
Area Under Concentration (AUC)	Area under the plasma concentration-time curve (AUC) of L19IL2 and ruxolitinib	Day 1, 2, 8, 15, 22, 23 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 5, and 6 (each cycle is 28 days)
Terminal Elimination Half-life (t½)	Terminal elimination half-life (t½) of L19IL2 and ruxolitinib	Day 1, 2, 8, 15, 22, 23 of Cycle 1 and Day 1 of Cycles 2, 3, 4, 5, and 6 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Philogen S.p.A.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: April 15, 2026
• First Submitted That Met QC Criteria: April 28, 2026
• First Posted (Actual): May 5, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Ruxolitinib; Advanced solid tumors
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; ruxolitinib
• Other Study ID Numbers: PH-L19IL2CORK-01/25; 2025-522243-17-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No