AzTrials
AzTrials

Melanoma Stage IIIPhase 2INTACT/MeRCINCT06284590

Study of the Efficacy of Intratumoral L19IL2 or L19TNF or L19IL2/L19TNF, in Combination With Pembrolizumab, in Unresectable Melanoma Patients

A Phase 2 study testing L19IL2, L19TNF and L19IL2/L19TNF in people with Melanoma Stage III and Melanoma Stage IV, run by Philogen S.p.A. at 7 sites in 3 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

The trial aims to evaluate the efficacy of single agent L19IL2, single agent L19TNF, and combination L19IL2+L19TNF given concurrently with anti-PD1 therapy compared to historical control of anti-PD-1 re-challenge alone for anti-PD1 refractory unresectable stage III-IV melanoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma Stage III, Melanoma Stage IV
What is being tested?
L19IL2, L19TNF and L19IL2/L19TNF
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
162 participants
Where
7 sitesin 3 countries
Study dates
12 Jul 2024to Jul 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
  • Be > or = 18 years of age on day of signing informed consent.
  • Participant with histologically or cytologically confirmed diagnosis of unresectable metastatic melanoma at stage III B, C, D or IV M1a (AJCC 8th ed.). Patients with Stage IVM1b, M1c and M1d oligometastatic disease [up to 10 visceral lesions in aggregate including lung, liver, bone or brain, with or without lymph node involvement], are eligible.
  • However, patients with symptomatic or rapidly enlarging/bleeding brain lesions are excluded. Patients with acral lentiginous melanoma are eligible as well. Detailed information about prior therapies and burden of disease at study entry must be available.
  • Patients must have confirmed primary resistance to or acquired resistance on treatment with an anti-PD1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:
  • Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
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  • Has demonstrated disease progression (PD) after PD-1/L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than four weeks from the date of the first documented PD, in the absence of rapid clinical progression.
  • Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb.
  • c.i. Progressive disease is determined according to iRECIST. c.ii. This determination is made by the investigator. Once PD is confirmed, the initial date of PD documentation will be considered the date of disease progression.
  • Patients harboring the BRAF mutation who received BRAF/MEK inhibition (or declined BRAF/MEK inhibitors) and received thereafter anti-PD1 therapy showing resistance to such immunotherapy are eligible to the study.
  • Eligible subjects must have measurable disease (according to RECIST v1.1) as assessed by the local site investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Eligible subjects must be candidates for intralesional therapy with at least one injectable cutaneous, subcutaneous, or nodal metastatic melanoma lesion (≥ 5 mm in longest diameter) or multiple injectable lesions that in aggregate have a diameter of ≥ 5 mm.
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
  • Not a woman of childbearing potential (WOCBP)
  • A WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment. WOCBP must be using for the time period indicated highly effective contraception methods. WOCBP and effective contraception methods are defined by the "Recommendations for contraception and pregnancy testing in clinical trials" issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group 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 or sexual abstinence. Pregnancy test will be repeated at the safety visit (only WOCBP).
  • Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
  • Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut (details pertaining to tumor tissue submission can be found in the Procedures Manual).
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Have adequate organ function. Specimens must be collected within 14 days prior to the start of study treatment.
  • Be able to provide a core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy at Screening. In addition, participants may provide additional biopsy at Week 18 and at the time of discontinuation due to progression.
  • Documented negative test for HIV, HBV and HCV. For HBV serology, the determination of HBsAg and anti-HBcAg Ab is required. In patients with serology documenting previous exposure to HBV (e.g. anti-HBsAg and/or anti-HBc Ab) a negative serum HBV-DNA test is also required.
  • All acute toxic effects (excluding alopecia and vitiligo) of any prior therapy must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v. 5.0) Grade ≤ 1 or baseline unless otherwise specified above.
  • Note: Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrinerelated AEs Grade ≤2 requiring treatment or hormone replacement may be eligible. Note: If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery before starting study intervention.
  • Full resolution of checkpoint blockade therapy-related adverse effects (including immunerelated adverse effects) and no treatment for these AEs for at least 4 weeks before the time of enrollment.
  • No history of severe immune related adverse effects from prior given immune checkpoint blockade therapy (CTCAE Grade 4; CTCAE Grade 3 requiring treatment >4 weeks).
  • 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 three months following the last study drug administration. In addition, male participant must refrain from sperm donation during the treatment period.
  • Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.

Who cannot join

  • Patients with more than 10 distant melanoma lesions in lung, liver, bone or brain combined. Patients with symptomatic or rapidly enlarging/bleeding brain lesions are excluded.
  • Uveal melanoma or mucosal melanoma or melanoma with unknown primary.
  • A WOCBP who has a positive urine pregnancy test (within 72 hours) prior to treatment.
  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, and was discontinued from that treatment due to a Grade 3 or higher irAE.
  • Has received prior systemic anti-cancer therapy including investigational agents or has used an investigational device within 4 weeks prior to the first dose of study treatment.
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  • Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
  • Has received prior radiotherapy within 2 weeks of start of study treatment or have had a history of radiation pneumonitis.
  • Note: Participants must have recovered from all radiation-related toxicities andnot require corticosteroids. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  • Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Participants who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of GVHD).
  • Has had an allogeneic tissue/solid organ transplant.
  • Has received live live or live attenuated vaccines within 30 days prior to the first dose of study treatment and while participating in the study. Note: Killed vaccines are allowed.
  • Note: Any licensed COVID-19 vaccine (including for Emergency use) in a particular country is allowed in the study as long as they are mRNA vaccines, adenoviral vaccines, or inactivated vaccines. These vaccines will be treated just as any other concomitant therapy.
  • Investigational vaccines (i.e., those not licensed or approved for Emergency Use) are not allowed.
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug.
  • Has a known additional malignancy that is progressing or has required active treatment within the past two (2) years.
  • Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder tumors (Ta, Tis \& T1), second primary melanoma in situ, or carcinoma in situ, that have undergone potentially curative therapy are not excluded.
  • Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients, or to (immuno)cytokines IL2, TNF and/or any of its excipients
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
  • Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease.
  • Has an active infection requiring systemic therapy.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  • Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
  • Previous enrolment and randomization in this same study.

Trial locations and contacts

7 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

Sheila Dakhel Plaza, PhD contact

+41 (0) 43 544 88 02

sheila.dakhel@philochem.ch

Concetta Aulicino contact

+39 057717816

regulatory@philogen.com

7 sites in 3 countries

Germany4 sites, 4 recruiting

  • Universitätsklinikum Essen

    Essen, Germany, 45147

    Dirk Schadendorf, +49-201-723-4342, dirk.schadendorf@uk-essen.de

    Dirk Schadendorf

    Recruiting

  • University of Freiburg, Faculty of Medicine

    Freiburg im Breisgau, Germany, 79104

    David Rafei-Shamsabadi, +49 761 270 67040, david.rafei-shamsabadi@uniklinik-freiburg.de

    David Rafei-Shamsabadi

    Recruiting

  • University Hospital Schleswig-Holstein

    Kiel, Germany, 24105

    Katharina Kähler, +49 431 500 21120, kkaehler@dermatology.uni-kiel.de

    Katharina Kahler

    Not yet recruiting

  • University Hospital Tuebingen

    Tübingen, Germany, 72076

    Lukas Flatz, +49 7071 29 84620, Lukas.Flatz@med.uni-tuebingen.de

    Lukas Flatz

    Not yet recruiting

Other trials in Germany

United States2 sites, 2 recruiting

  • Hartford Hospital

    Hartford, Connecticut, 06102

    Jaykumar Thumar, MD

    Jaykumar Thumar, MD

    Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Danielle Marie Bello, MD, bellod@mskcc.org

    Danielle Marie Bello, MD

    Recruiting

Other trials in United States

Italy1 site, 1 recruiting

  • IRCCS Istituto Nazionale Tumori "Fondazione Giovanni Pascale"

    Naples, Campania, 80131

    Paolo Ascierto, +39 08117770443, p.ascierto@istitutotumori.na.it

    Paolo Ascierto

    Recruiting

Other trials in Italy

About this study

Official title: A Phase 2, Three-arm, Randomized Study of the Efficacy of Intratumorally Administered L19IL2 or L19TNF or L19IL2/L19TNF, All in Combination With Systemic Anti-PD1 Pembrolizumab, in Stage III and IV Unresectable Melanoma Patients With Resistance to or Progressing Upon Anti-PD1 Checkpoint Inhibitors and With Presence of Injectable Metastases

The trial aims to evaluate the efficacy of single agent L19IL2, single agent L19TNF, and combination L19IL2+L19TNF given concurrently with anti-PD1 therapy compared to historical control of anti-PD-1 re-challenge alone for anti-PD1 refractory unresectable stage III-IV melanoma.

Read the detailed description

The present study is a randomized, open-label, three-arm, parallel phase 2 study. A Simon two-stage design for the study of the efficacy of intralesional therapy with L19IL2 or L19TNF or L19IL2/L19TNF in combination with systemic anti-PD1 pembrolizumab immunotherapy will be used.

In the study, 162 patients will be randomized in a 1:1:1 ratio to receive:

  1. systemic pembrolizumab in combination with intralesional L19IL2 (Arm 1) or ii) systemic pembrolizumab in combination with intralesional L19TNF (Arm 2) or iii) systemic pembrolizumab in combination with intralesional L19IL2/L19TNF (Arm 3).

This is an open-label study, so there is no blinding.

The study consists of a two-week screening period, followed by a 4-weeks open-label intralesional treatment period with immunocytokines (ICKs) either L19IL2, L19TNF or L19IL2/L19TNF. Pembrolizumab will be administered by i.v. infusion on the first day of intralesional treatment with ICKs, and will continue every 3 weeks for approximately 2 years, 35 cycles, 2 year cap or until disease progression or unacceptable toxicity, whichever comes first.

Follow-up for progression free survival will be performed up to 2 years after first intralesional treatment. Survival information will be collected up to 3 years after first intralesional treatment.

A safety run-in will be performed on the first 12 patients enrolled in each arm of the study. Patients will be evaluated during the first 21-days cycle for the occurrence of the treatment-related adverse events. All toxicities will be graded using NCI CTCAE Version 5.0 based on the investigator assessment to be possibly, probably, or definitely related to study treatment administration.

In addition to this, safety information collected will be routinely reviewed by the Data and Safety Monitoring Board (DSMB) in order to identify possible safety concerns.

The primary objective of the study is to demonstrate the efficacy of intralesional treatment with ICKs, in combination with systemic anti-PD1 immunotherapy with pembrolizumab, to induce objective responses in advanced melanoma patients with resistance to or progressing upon anti-PD1 checkpoint inhibitors.

Primary endpoint of the study is the Confirmed Objective Response Rate (ORR = CR + PR) in all three arms over a period of up to 2 years after first intralesional treatment, according to RECIST v1.1 criteria in each arm of the study. The primary analysis will be performed in the Intention-to-Treat population (ITT).

For each of the three treatment arms, secondary objectives include efficacy and safety of intralesional treatment with ICKs.

The secondary endpoints include:

  • Best overall response (BOR; the best overall response is the best response recorded from the start of the treatment until disease progression/recurrence according to RECIST v1.1 criteria)
  • Duration of response (DoR)
  • Pathological response of one target lesion injected with ICKs at 18 weeks after first treatment
  • Confirmed ORR over a period of up to 2 years after first intralesional treatment, according to iRECIST (see Appendix 1) and itRECIST [1] criteria in each arm of the study
  • Progression-free survival (PFS) from time of randomization
  • Overall survival (OS) from randomization
  • Number, frequency and grading of adverse events (AEs) and serious adverse events (SAEs) related to intralesional therapy with ICKs in combination with systemic anti-PD1 therapy

End of treatment: last day of anti-PD1 therapy or until progression or unacceptable toxicity.

End of study: corresponds to the last patient last visit (LPLV).

Being tested
L19IL2, L19TNF, L19IL2/L19TNF, KEYTRUDA®
Keywords
anti-PD1 checkpoint inhibitors, Melanoma Stage III, Melanoma Stage IV, pembrolizumab
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • L19IL2Drug

    Also called bifikafusp alfa

    Arm 1: The amount of L19IL2 that is intratumorally administered into injectable cutaneous, subcutaneous, and nodal tumors once weekly for up to 4 weeks is dependent on the size of the tumor. The maximum dose to be administered in a single treatment visit is 13 MioIU/1 mL of L19IL2.

  • L19TNFDrug

    Also called onfekafusp alfa

    Arm 2: The amount of L19TNF that is intratumorally administered into injectable cutaneous, subcutaneous, and nodal tumors once weekly for up to 4 weeks is dependent on the size of the tumor. The maximum dose to be administered in a single treatment visit is 400 μg/1 mL of L19TNF.

  • L19IL2/L19TNFDrug

    Also called Daromun

    Arm 3: The amount of L19IL2/L19TNF that is intratumorally administered into injectable cutaneous, subcutaneous, and nodal tumors once weekly for up to 4 weeks is dependent on the size of the tumor. The maximum dose to be administered in a single treatment visit is 13MioIU L19IL2 + 400 μg L19TNF in a combined total volume of approximate 2 mL. In case that study drug-related, grade ≥ γ AEs are recorded after the first L19IL2/L19TNF dose administration, the L19TNF dose is reduced to 200 μg for the following administrations.

  • KEYTRUDA®Drug

    Also called pembrolizumab

    KEYTRUDA® will be administered by i.v. infusion as a dose of 200 mg on the first day of intralesional treatment with ICKs and will continue every 3 weeks for approximately 2 years, 35 cycles, 2 year cap or until disease progression or unacceptable toxicity, whichever comes first. ICKs intralesional treatment will be administered 30-60 minutes post administration of KEYTRUDA®.

Study groups in NCT06284590
Study groupRoleWhat they receive
Systemic pembrolizumab in combination with intralesional L19IL2 (Arm 1)ExperimentalTwo-weeks screening period and a 4-weeks open-label intralesional treatment period with L19IL2. Pembrolizumab will be administered by i.v. infusion on the first day of intralesional treatment with L19IL2, and will continue every 3 weeks for approximately 2 years, 35 cycles, 2 year cap or until disease progression or unacceptable toxicity, whichever comes first.
Receives: Drug: L19IL2; Drug: KEYTRUDA®
Systemic pembrolizumab in combination with intralesional L19TNF (Arm 2)ExperimentalTwo-weeks screening period and a 4-weeks open-label intralesional treatment period with L19TNF. Pembrolizumab will be administered by i.v. infusion on the first day of intralesional treatment with L19TNF, and will continue every 3 weeks for approximately 2 years, 35 cycles, 2 year cap or until disease progression or unacceptable toxicity, whichever comes first.
Receives: Drug: L19TNF; Drug: KEYTRUDA®
Systemic pembrolizumab in combination with intralesional L19IL2/L19TNF (Arm 3)ExperimentalTwo-weeks screening period and a 4-weeks open-label intralesional treatment period with L19IL2/L19TNF. Pembrolizumab will be administered by i.v. infusion on the first day of intralesional treatment with L19IL2/L19TNF, and will continue every 3 weeks for approximately 2 years, 35 cycles, 2 year cap or until disease progression or unacceptable toxicity, whichever comes first.
Receives: Drug: L19IL2/L19TNF; Drug: KEYTRUDA®

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Confirmed Objective Response Rate (ORR)

    Objective Response Rate (ORR = CR + PR) in all three arms to demonstrate the efficacy of intralesional treatment with immunocytokines (L19IL2, or L19TNF, or L19IL2/L19TNF), in combination with the systemic anti-PD1 pembrolizumab, to induce objective responses in advanced melanoma patients with resistance to or progressing upon anti-PD1 checkpoint inhibitors. The primary analysis will be performed in the Intention-to-Treat population (ITT).

    Assessed during Tumor Assessment (TA) visits.

    Measured: Evaluated over a period of up to 2 years after first intralesional treatment. TA visits will be performed at week 12, 18, 24, 36, 48, 64, 80 and 96 after first intralesional treatment or until confirmed progression or death, whichever occurs first

Secondary outcomes (27)

  1. Best overall response (BOR)

    Best response recorded from the start of the treatment until disease progression/recurrence after first treatment according to RECIST v1.1 criteria

    Measured: From the date of first treatment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 96 Weeks

  2. Duration of Response (DoR)

    Time from first documented evidence of CR or PR until first documented disease progression or death due to any cause. DoR will be summarized descriptively using Kaplan-Meier medians and quartiles.

    Measured: From the date of first treatment until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 36 Months

  3. Pathological response

    Histopathological analysis will be performed on biopsies obtained at baseline and at Week 18 for one target injected lesions.

    This is to determine:

    • Confirmation of melanoma metastasis( Biopsy at baseline)
    • Presence of residual tumor cells (%, biopsy at week 18),
    • Presence of Necrosis % (biopsy at week 18),
    • Presence of melanosis/fibrosis % (biopsy at weeks 18 after first treatment)

    Measured: At 18 weeks after first treatment

  4. Confirmed ORR

    Confirmed ORR over a period of up to 2 years after first intralesional treatment according to iRECIST and itRECIST criteria in each arm of the study

    Measured: From date of first administration, after a period of up to 2 years

  5. Progression-free survival (PFS)

    Difference between date of randomization and the date of progression according to RECIST v. 1.1 criteria or death

    Measured: From the date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 96 Weeks

  6. Overall survival (OS)

    Difference between date of randomization and the date of death for any cause

    Measured: From the date of randomization until the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 96 Weeks

  7. Adverse Events (AEs) and Serious Adverse Event (SAEs)

    Percentage of Patients in Each Treatment Group with Drug-Related Adverse Events, Serious Adverse Event (SAEs)

    Measured: From date of ICF signature until first follow-up visit (Week 12). Subsequently only AEs and SAEs (and related medications or procedures) that were judged as drug or study related will be recorded, up to week 96

  8. Drug-Induced Liver Injury (DILI)

    Number of patients with Drug-Induced Liver Injury (DILI)

    Measured: From date of ICF signature until first follow-up visit (Week 12). Subsequently only DILI that were judged as drug or study related will be recorded, up to week 96

  9. Adverse Events of Special Interest (AESI)

    Number of patients with Adverse Events of Special Interest (AESI)

    Measured: From date of ICF signature until first follow-up visit (Week 12). Subsequently only AESI that were judged as drug or study related will be recorded, up to week 96

  10. Immune-Related Adverse Events (IRAEs)

    Number of patients with Immune-Related Adverse Events (IRAEs)

    Measured: From date of ICF signature until first follow-up visit (Week 12). Subsequently only IRAEs that were judged as drug or study related will be recorded, up to week 96

  11. Abnormal hematology laboratory tests results: Red Blood Cells

    Number of participants with abnormal hematology laboratory tests results: red blood cells; Millions/microliter (M/mcL)

    Measured: From the screening to the last visit (Week 103)

  12. Abnormal hematology laboratory tests results: Neutrophil, White Blood Cells, Platelet, Differential

    Number of participants with abnormal hematology laboratory tests results: Count of absolute neutrophil (ANC), White Blood cells (WBC), Platelet, Differential; thousands/microliter (K/mcL)

    Measured: From the screening to the last visit (Week 103)

  13. Abnormal hematology laboratory tests results: Hematocrit

    Number of participants with abnormal hematology laboratory tests results: Hematocrit; percent (%)

    Measured: From the screening to the last visit (Week 103)

  14. Abnormal hematology laboratory tests results: Hemoglobin

    Number of participants with abnormal hematology laboratory tests results: Hemoglobin; grams/deciliter (g/dL)

    Measured: From the screening to the last visit (Week 103)

  15. Abnormal serum chemistry laboratory tests results: Creatinine, Blood Urea Nitrogen or Urea, Uric acid, Calcium, Glucose, Phosphorus, Magnesium

    Number of participants with abnormal serum chemistry laboratory tests results: Creatinine, Blood Urea Nitrogen or Urea, Uric acid, Calcium, Glucose, Phosphorus, Magnesium; milligrams/deciliter (mg/dL)

    Measured: From the screening to the last visit (Week 103)

  16. Abnormal serum chemistry laboratory tests results: Potassium, Sodium, Chloride

    Number of participants with abnormal serum chemistry laboratory tests results: Potassium, Sodium, Chloride; milliequivalents/liter (mEq/L)

    Measured: From the screening to the last visit (Week 103)

  17. Abnormal serum chemistry laboratory tests results: Total proteins, Albumin

    Number of participants with abnormal serum chemistry laboratory tests results: Total proteins, Albumin; grams/deciliter (g/dL)

    Measured: From the screening to the last visit (Week 103)

  18. Abnormal serum chemistry laboratory tests results: Lactate dehydrogenase (LDH)

    Number of participants with abnormal serum chemistry laboratory tests results: Lactate dehydrogenase (LDH); units/liter (U/L)

    Measured: From the screening to the last visit (Week 103)

  19. Abnormal serum chemistry laboratory tests results: Adrenocorticotropic Hormone (ACTH)

    Number of participants with abnormal serum chemistry laboratory tests results: Adrenocorticotropic Hormone (ACTH); picograms/milliliter (pg/ml)

    Measured: From the screening to the last visit (Week 103)

  20. Abnormal coagulation laboratory tests results: Prothrombin Time PT or PT INR, PTT or aPTT

    Number of participants with abnormal coagulation laboratory tests results: Prothrombin Time PT or PT INR, PTT or aPTT; seconds (sec)

    Measured: From the screening to the last visit (Week 103)

  21. Abnormal body temperature

    Number of participants with abnormal body temperature (degree centigrade)

    Measured: From the screening to the last visit (Week 103)

  22. Abnormal blood pressure

    Number of participants with abnormal blood pressure: Systolic and diastolic blood pressure (after 3 minutes in sitting position); mmHg

    Measured: From the screening to the last visit (Week 103)

  23. Abnormal Electrocardiogram (ECG) readings

    Number of participants with abnormal Electrocardiogram (ECG) readings: Heart rate, standard intervals (PR, QRS, QT, and QTc) and any observed abnormality; millisecond

    Measured: At the screening visit, at Visit 6 (week 5) and at Visit 12 (week 18)

  24. Abnormal Echocardiogram (ECHO) readings

    Number of participants with abnormal Echocardiogram (ECHO) readings: Morphological and functional aspects of the heart. Left Ejection Fraction (LVEF) is determined; percentage %

    Measured: At the screening visit, at Visit 6 (week 5) and at Visit 12 (week 18)

  25. Abnormal physical examination results

    Number of participants with abnormal physical examination results

    Measured: From the screening to first follow up visit

  26. Concomitant medication usage

    Concomitant medication usage

    Measured: From the screening and throughout study

  27. Human anti-fusion protein antibodies (HAFA)

    Assessment of the formation of human anti-fusion protein antibodies (HAFA) against L19IL2 and L19TNF

    Measured: At weeks 1, 2 and 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Feb 2024
  2. Study start12 Jul 2024
  3. Primary completionJul 2028 (estimated)
  4. Study completionJul 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
162 patients. Patients enrolled will be randomized in a 1:1:1 ratio. i) systemic pembrolizumab in combination with intralesional L19IL2 (Arm 1): 54 patients. ii) systemic pembrolizumab in combination with intralesional L19TNF (Arm 2): 54 patients iii) systemic pembrolizumab in combination with intralesional L19IL2/L19TNF (Arm 3): 54 patients
Masking
None (open label)
Enrolment
162 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06284590
Sponsor's protocol ID
PH-ICKPD1-02/21
Other IDs
2024-519326-20-00, MK-3475-F20, KEYNOTE-F20
Acronym
INTACT/MeRCI
Status last verified
Aug 2026
First submitted
26 Jan 2024
Last updated
2 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing L19IL2, L19TNF and L19IL2/L19TNF in people with Melanoma Stage III and Melanoma Stage IV, run by Philogen S.p.A. at 7 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Germany, United States, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Sheila Dakhel Plaza, PhD (+41 (0) 43 544 88 02, sheila.dakhel@philochem.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Confirmed Objective Response Rate (ORR) (time frame: Evaluated over a period of up to 2 years after first intralesional treatment. TA visits will be performed at week 12, 18, 24, 36, 48, 64, 80 and 96 after first intralesional treatment or until confirmed progression or death, whichever occurs first). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06284590.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.

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