Malignant MelanomaPhase 3PivotalNCT02938299
Neoadjuvant L19IL2/L19TNF- Pivotal Study
A Phase 3 study testing L19IL2 + L19TNF and Surgery in people with Malignant Melanoma, run by Philogen S.p.A. at 22 sites in 4 countries.
Trial summary
Phase III, open-label, randomized, controlled multi-center study of the efficacy of L19IL2/L19TNF neoadjuvant intratumoral treatment in Stage III B/C melanoma patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Melanoma
- What is being tested?
- L19IL2 + L19TNF and Surgery
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 214 participants
- Where
- 22 sitesin 4 countries
- Study dates
- 1 Jul 2016to Dec 2028
- Phase
- Phase 3
- 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
- Diagnosis of malignant melanoma of the skin with locally advanced disease as defined by clinical stage III B and III C according to AJCC 7th Ed., eligible for complete surgical resection.
- Eligible subjects must have measurable disease and must be candidate for intralesional therapy with at least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (≥ 10 mm in longest diameter) or with multiple injectable lesions that in aggregate have a longest diameter of ≥ 10 mm.
- Prior anti-tumor treatment for the primary melanoma lesion, including surgery and approved adjuvant treatments (e.g., radiotherapy, immune checkpoint inhibitors, BRAF/MEK inhibitors, etc.) is allowed.
- Males or females, age ≥ 18 years.
- ECOG Performance Status/WHO Performance Status ≤ 1.
- Life expectancy of at least 24 months (see paragraph 6.3.1).
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- Absolute neutrophil count > 1.5 x 109/L.
- Hemoglobin > 9.0 g/dL.
- Platelets > 100 x 109/L.
- Total bilirubin ≤ 30 µmol/L (or ≤ 2.0 mg/dl).
- ALT and AST ≤ 2.5 x the upper limit of normal (ULN).
- Serum creatinine < 1.5 x ULN.
- LDH serum level ≤ 1.5 x ULN.
- 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) negative serum HBV-DNA is also required.
- All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v4.03) Grade ≤ 1 unless otherwise specified above.
- Negative pregnancy test at screening for Women Of Childbearing Potential (WOCBP*). Pregnant women are not allowed to participate to this study. WOCBP must be using, from the screening to three months following the last study drug 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 or sexual abstinence. Pregnancy test will be repeated at the Safety Visit (only WOCBP and only for patients in Arm 1).
- 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.
- Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of 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).
Who cannot join
- Uveal melanoma, mucosal melanoma or melanoma with unknown primary.
- Evidence of distant metastases at screening.
- Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis \& T1), second primary melanoma in situ or any cancer curatively treated ≥ 5 years prior to study entry.
- Presence of active infections (e.g., requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.
- History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
- Inadequately controlled cardiac arrhythmias including atrial fibrillation.
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- Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).
- LVEF ≤ 50% and/or abnormalities observed during baseline ECG and Echocardiogram investigations that are considered as clinically significant by the investigator.
- Uncontrolled hypertension.
- Ischemic peripheral vascular disease (Grade IIb-IV).
- Severe diabetic retinopathy.
- Active autoimmune disease.
- History of organ allograft or stem cell transplantation.
- Recovery from major trauma including surgery within 4 weeks prior to enrollment.
- Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies or any other constituent of the product.
- Breast feeding female.
- Anti-tumor therapy (except allowed treatments listed at point 3 of Inclusion criteria) within 4 weeks before enrollment.
- Previous in vivo exposure to monoclonal antibodies for biological therapy (except allowed treatments listed at point 3 of Inclusion criteria) in the 6 weeks before enrollment.
- Planned administration of growth factors or immunomodulatory agents (except allowed treatments listed at point 3 of Inclusion criteria) within 7 days before enrollment.
- Patient requiring or taking corticosteroids or other immunosuppressant drugs on a long-term basis. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criterion.
- Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.
- Previous enrolment and randomization in this same study.
Trial locations and contacts
22 sites in 4 countries.
22 sites in 4 countries
Germany10 sites
Klinik für Dermatologie und Allergologie, Universitätsklinikum Augsburg
Augsburg, 86156
Charité Campus Mitte (CCM)
Berlin, State of Berlin, D-10117
Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden
Dresden, Dresden, D-01307
Klinik für Dermatologie, Medizinische Fakultät Universitätsklinikum Essen
Essen, 45122
Hauttumorzentrum Hannover (HTZH)
Hanover, Hannover, D-30625
Heidelberg University Hospital
Heidelberg, Heidelberg, D-69120
Kiel University Hospital
Kiel, Kiel, D-24105
Leipzig University Hospital
Leipzig, Leipzig, D-04103
Klinik und Polyklinik für Dermatologie, Universitätsklinikum Regensburg
Regensburg, 93042
Tübingen University Hospital
Tübingen, Tübingen, D-72076
Italy7 sites
IRCCS A.O.U. San Martino - IST
Genova, Genova, 16132
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Milan, 20133
Fondazione IRCCS Istituto Nazionale dei Tumori
Naples, 80131
Istituto Oncologico Veneto, IRCCS
Padova, Padova, 35128
AOU Senese
Siena, 53100
ASUGI Trieste
Trieste, 34128
AOU Città della Salute e della Scienza
Turin, 10126
France3 sites
Hôpital de la Timone
Marseille, 13 005
Hôpital Universitaire de Nantes
Nantes, 44 093
Institut Gustave Roussy
Villejuif, 94 805
Poland2 sites
Medgart Centrum Medyczne
Gdansk, 80-980
Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie Warszawa
Warsaw, 02-781
About this study
Official title: A Pivotal Phase III, Open-label, Randomized, Controlled Multi-center Study of the Efficacy of L19IL2/L19TNF Neoadjuvant Intratumoral Treatment Followed by Surgery Versus Surgery Alone in Clinical Stage III B/C Melanoma Patients
Phase III, open-label, randomized, controlled multi-center study of the efficacy of L19IL2/L19TNF neoadjuvant intratumoral treatment in Stage III B/C melanoma patients.
Read the detailed description
Phase III, open-label, randomized, controlled multi-center study. In the study, 214 patients will be enrolled and parallel assigned (via automated randomization system) in a 1:1 fashion to one of two different arms:
ARM 1:
Patients in Arm 1 will receive multiple intratumoral administrations into all injectable cutaneous, subcutaneous, and nodal tumors of a mixture of L19IL2 and L19TNF once weekly for up to 4 weeks (or until all injectable tumors have disappeared, or intolerance to study treatment or in the opinion of the investigator immediate surgical resection or any other treatment for melanoma is warranted, whichever occurs first). The whole volume of L19IL2/L19TNF will be distributed among all injectable lesions.
Newly occurring injectable melanoma lesions within the 4 weeks treatment period will also be treated as described. For the new lesions the treatment period will not be extended beyond the pre-defined 4 week- treatment period with a clock start at the time of the first intralesional L19IL2/L19TNF injection. Surgical resection of all existing metastases will follow within 4 weeks after end of treatment. Surgery will be performed after the safety evaluation carried out at week 5 and, if indicated, may be carried out on the same day of the safety evaluation.
Post-surgery EMA-approved adjuvant therapy is allowed at discretion of the treating physician.
ARM 2:
Patients in Arm 2 will receive directly surgical resection of melanoma tumor lesions within 4 weeks after randomization.
Post-surgery EMA-approved adjuvant therapy is allowed at discretion of the treating physician.
Patients will be followed on a regular basis for the primary outcome until 36 months from randomization and up to 60 months for overall survival.
Expected patient enrollment interval: 60 months. Duration of individual patient's participation: up to 60 months. End of treatment corresponds to the day of surgery for patients randomized to both Arm 1 and Arm 2.
End of study corresponds to the last patient last visit (LPLV). The final primary efficacy analysis will be conducted when the 95th recurrence event is observed.
- Conditions
- Malignant Melanoma
- Being tested
- L19IL2 + L19TNF, Surgery
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L19IL2 + L19TNFDrug
Mixture of L19IL2 and L19TNF once weekly
SurgeryProcedure or surgery
Surgical resection of melanoma tumor lesions
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: neoadjuvant + surgery | Experimental | Patients in Arm 1 will receive multiple intratumoral administrations into all injectable cutaneous, subcutaneous, and nodal tumors of a mixture of L19IL2 and L19TNF once weekly for up to 4 weeks (or until all injectable tumors have disappeared, or intolerance to study treatment or in the opinion of the investigator immediate surgical resection or any other treatment for melanoma is warranted, whichever occurs first).
Newly occurring injectable melanoma lesions within the 4 weeks treatment period will also be treated as described. Surgical resection of all existing metastases will follow within 4 weeks after end of treatment. Surgery will be performed after the safety evaluation carried out at week 5 and, if indicated, may be carried out on the same day of the safety evaluation. Receives: Drug: L19IL2 + L19TNF; Procedure: Surgery |
| Arm 2: surgery alone | Active comparator | Patients in Arm 2 will receive directly surgical resection of melanoma tumor lesions within 4 weeks after randomization. Receives: Procedure: Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence-free survival (RFS) rate
Recurrence-free survival (RFS) in the treatment arm (L19IL2/L19TNF plus surgery; Arm 1) versus control arm (Arm 2).
Measured: 1 year after randomization
Secondary outcomes (9)
Local recurrence-free survival (LRFS)
Measured: 1year, 2years, 3years after randomization and 1year after surgery
Distant metastasis-free survival (DMFS) rate
Measured: 1year, 2years, 3years after randomization and 1year after surgery
Recurrence-free survival (RFS) rate
Measured: 2years, 3years after randomization
Overall survival (OS)
Measured: 1year, 2years, 3years after randomization
Percentage of Participants With On-Study Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: up to 3 years
Percentage of Participants With Worst On-Study Hematological and Chemistry Abnormalities
Measured: up to 36 months
Clinically Meaningful Changes in Vital Signs and Physical Examinations
Measured: up to 36 months
Changes in absolute counts and relative percentages of lymphocytic subpopulations over time
Immunophenotypic characterization of PBMCs for changes in absolute counts and relative percentages of lymphocytic subpopulations (e.g., Tregs, MDSCs etc.) over time (only for patients recruited in German centers).
Measured: (1) At screening, (2) At Day of surgery: from Day 1 to Day 54, (3) After 3 months from surgery: Day 91 to Day 144
HAFA
Assessment of the formation of human anti-fusion protein antibodies (HAFA) against L19IL2 and L19TNF.
Measured: (1) At Day 1, (2) At Day 29, (3) After 3 months from surgery: Day 119 to Day 144
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2016 (estimated)
- Study start1 Jul 2016
- Primary completionOct 2024 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 214 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Philogen S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Katharina C. Kähler, MD, Principal investigator, University Hospital Schleswig-HolsteinMario Santinami, MD, Principal investigator, Istituto Nazionale Tumori MilanoPiotr Rutkowski, MD, Principal investigator, Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie WarszawaCaroline Robert, MD, Principal investigator, Gustave Roussy, Cancer Campus, Grand Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02938299
- Sponsor's protocol ID
- PH-L19IL2TNF-02/15
- Acronym
- Pivotal
- Status last verified
- Sep 2024
- First submitted
- 11 Oct 2016
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Hauschild A, Hassel JC, Ziemer M, Rutkowski P, Meier F, Flatz L, Gaudy-Marqueste C, Santinami M, Russano F, von Wasielewski I, Eigentler T, Maio M, Zalaudek I, Haferkamp S, Quaglino P, Welzel J, Weichenthal M, Elia G, Covelli A, Lorizzo K, Parca A, Neri D, Ascierto PA, Robert C, Schadendorf D, Kaehler KC. Neoadjuvant Intralesional Daromun (L19IL2/L19TNF) in Resectable Locally Advanced Melanoma: An Update on the Efficacy and Safety Results of the PIVOTAL Phase III Trial. J Clin Oncol. 2026 Aug 11:JCO2600852. doi: 10.1200/JCO-26-00852. Online ahead of print.
PubMed 42579833Kahler KC, Hassel JC, Ziemer M, Rutkowski P, Meier F, Flatz L, Gaudy-Marqueste C, Zimmer L, Santinami M, Russano F, von Wasielewski I, Eigentler TK, Maio M, Zalaudek I, Haferkamp S, Quaglino P, Welzel J, Rocken C, Enk A, Simon JC, Switaj T, Garzarolli M, Amaral T, Malissen N, Livingstone E, Elia G, Covelli A, Lorizzo K, Neri D, Mulatto S, Parca A, Pizzichi B, Ascierto PA, Garbe C, Robert C, Schadendorf D, Hauschild A. Neoadjuvant intralesional targeted immunocytokines (daromun) in stage III melanoma. Ann Oncol. 2025 Oct;36(10):1166-1177. doi: 10.1016/j.annonc.2025.06.014. Epub 2025 Jul 7.
PubMed 40633690Gorry C, McCullagh L, O'Donnell H, Barrett S, Schmitz S, Barry M, Curtin K, Beausang E, Barry R, Coyne I. Neoadjuvant treatment for stage III and IV cutaneous melanoma. Cochrane Database Syst Rev. 2023 Jan 17;1(1):CD012974. doi: 10.1002/14651858.CD012974.pub2.
PubMed 36648215
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pivotal Phase III, Open-label, Randomized, Controlled Multi-center Study of the Efficacy of L19IL2/L19TNF Neoadjuvant Intratumoral Treatment Followed by Surgery Versus Surgery Alone in Clinical Stage III B/C Melanoma Patients
- ClinicalTrials.gov ID
- NCT02938299
- Acronym / sponsor ID
- Pivotal / PH-L19IL2TNF-02/15
- Conditions
- Malignant Melanoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 214 participants (estimated)
- Lead sponsor
- Philogen S.p.A.Industry (pharma, biotech, devices)
- Study start
- 1 Jul 2016 (actual)
- Primary completion
- Oct 2024 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 19 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase III, open-label, randomized, controlled multi-center study of the efficacy of L19IL2/L19TNF neoadjuvant intratumoral treatment in Stage III B/C melanoma patients.
Detailed description
Phase III, open-label, randomized, controlled multi-center study. In the study, 214 patients will be enrolled and parallel assigned (via automated randomization system) in a 1:1 fashion to one of two different arms:
ARM 1:
Patients in Arm 1 will receive multiple intratumoral administrations into all injectable cutaneous, subcutaneous, and nodal tumors of a mixture of L19IL2 and L19TNF once weekly for up to 4 weeks (or until all injectable tumors have disappeared, or intolerance to study treatment or in the opinion of the investigator immediate surgical resection or any other treatment for melanoma is warranted, whichever occurs first). The whole volume of L19IL2/L19TNF will be distributed among all injectable lesions.
Newly occurring injectable melanoma lesions within the 4 weeks treatment period will also be treated as described. For the new lesions the treatment period will not be extended beyond the pre-defined 4 week- treatment period with a clock start at the time of the first intralesional L19IL2/L19TNF injection. Surgical resection of all existing metastases will follow within 4 weeks after end of treatment. Surgery will be performed after the safety evaluation carried out at week 5 and, if indicated, may be carried out on the same day of the safety evaluation.
Post-surgery EMA-approved adjuvant therapy is allowed at discretion of the treating physician.
ARM 2:
Patients in Arm 2 will receive directly surgical resection of melanoma tumor lesions within 4 weeks after randomization.
Post-surgery EMA-approved adjuvant therapy is allowed at discretion of the treating physician.
Patients will be followed on a regular basis for the primary outcome until 36 months from randomization and up to 60 months for overall survival.
Expected patient enrollment interval: 60 months. Duration of individual patient's participation: up to 60 months. End of treatment corresponds to the day of surgery for patients randomized to both Arm 1 and Arm 2.
End of study corresponds to the last patient last visit (LPLV). The final primary efficacy analysis will be conducted when the 95th recurrence event is observed.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: neoadjuvant + surgery | Experimental | Drug: L19IL2 + L19TNF, Procedure: SurgeryPatients in Arm 1 will receive multiple intratumoral administrations into all injectable cutaneous, subcutaneous, and nodal tumors of a mixture of L19IL2 and L19TNF once weekly for up to 4 weeks (or until all injectable tumors have disappeared, or intolerance to study treatment or in the opinion of the investigator immediate surgical resection or any other treatment for melanoma is warranted, whichever occurs first). Newly occurring injectable melanoma lesions within the 4 weeks treatment period will also be treated as described. Surgical resection of all existing metastases will follow within 4 weeks after end of treatment. Surgery will be performed after the safety evaluation carried out at week 5 and, if indicated, may be carried out on the same day of the safety evaluation. |
| Arm 2: surgery alone | Active comparator | Procedure: SurgeryPatients in Arm 2 will receive directly surgical resection of melanoma tumor lesions within 4 weeks after randomization. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Diagnosis of malignant melanoma of the skin with locally advanced disease as defined by clinical stage III B and III C according to AJCC 7th Ed., eligible for complete surgical resection.
- Eligible subjects must have measurable disease and must be candidate for intralesional therapy with at least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (≥ 10 mm in longest diameter) or with multiple injectable lesions that in aggregate have a longest diameter of ≥ 10 mm.
- Prior anti-tumor treatment for the primary melanoma lesion, including surgery and approved adjuvant treatments (e.g., radiotherapy, immune checkpoint inhibitors, BRAF/MEK inhibitors, etc.) is allowed.
- Males or females, age ≥ 18 years.
- ECOG Performance Status/WHO Performance Status ≤ 1.
Key exclusion criteria (22 listed)
- Uveal melanoma, mucosal melanoma or melanoma with unknown primary.
- Evidence of distant metastases at screening.
- Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta, Tis \& T1), second primary melanoma in situ or any cancer curatively treated ≥ 5 years prior to study entry.
- Presence of active infections (e.g., requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.
- History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L19IL2 + L19TNFMixture of L19IL2 and L19TNF once weekly | Drug | Arm 1: neoadjuvant + surgery |
| SurgerySurgical resection of melanoma tumor lesions | Procedure or surgery | Arm 1: neoadjuvant + surgery, Arm 2: surgery alone |
Primary outcome
Recurrence-free survival (RFS) rate
Time frame: 1 year after randomization
Recurrence-free survival (RFS) in the treatment arm (L19IL2/L19TNF plus surgery; Arm 1) versus control arm (Arm 2).
9 secondary outcomes
Local recurrence-free survival (LRFS)
Time frame: 1year, 2years, 3years after randomization and 1year after surgery
Distant metastasis-free survival (DMFS) rate
Time frame: 1year, 2years, 3years after randomization and 1year after surgery
Recurrence-free survival (RFS) rate
Time frame: 2years, 3years after randomization
Overall survival (OS)
Time frame: 1year, 2years, 3years after randomization
Percentage of Participants With On-Study Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: up to 3 years
Percentage of Participants With Worst On-Study Hematological and Chemistry Abnormalities
Time frame: up to 36 months
Clinically Meaningful Changes in Vital Signs and Physical Examinations
Time frame: up to 36 months
Changes in absolute counts and relative percentages of lymphocytic subpopulations over time
Time frame: (1) At screening, (2) At Day of surgery: from Day 1 to Day 54, (3) After 3 months from surgery: Day 91 to Day 144
HAFA
Time frame: (1) At Day 1, (2) At Day 29, (3) After 3 months from surgery: Day 119 to Day 144
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Derived from this study: PubMed 42579833Hauschild A, Hassel JC, Ziemer M, Rutkowski P, Meier F, Flatz L, Gaudy-Marqueste C, Santinami M, Russano F, von Wasielewski I, Eigentler T, Maio M, Zalaudek I, Haferkamp S, Quaglino P, Welzel J, Weichenthal M, Elia G, Covelli A, Lorizzo K, Parca A, Neri D, Ascierto PA, Robert C, Schadendorf D, Kaehler KC. Neoadjuvant Intralesional Daromun (L19IL2/L19TNF) in Resectable Locally Advanced Melanoma: An Update on the Efficacy and Safety Results of the PIVOTAL Phase III Trial. J Clin Oncol. 2026 Aug 11:JCO2600852. doi: 10.1200/JCO-26-00852. Online ahead of print.
- Derived from this study: PubMed 40633690Kahler KC, Hassel JC, Ziemer M, Rutkowski P, Meier F, Flatz L, Gaudy-Marqueste C, Zimmer L, Santinami M, Russano F, von Wasielewski I, Eigentler TK, Maio M, Zalaudek I, Haferkamp S, Quaglino P, Welzel J, Rocken C, Enk A, Simon JC, Switaj T, Garzarolli M, Amaral T, Malissen N, Livingstone E, Elia G, Covelli A, Lorizzo K, Neri D, Mulatto S, Parca A, Pizzichi B, Ascierto PA, Garbe C, Robert C, Schadendorf D, Hauschild A. Neoadjuvant intralesional targeted immunocytokines (daromun) in stage III melanoma. Ann Oncol. 2025 Oct;36(10):1166-1177. doi: 10.1016/j.annonc.2025.06.014. Epub 2025 Jul 7.
- Derived from this study: PubMed 36648215Gorry C, McCullagh L, O'Donnell H, Barrett S, Schmitz S, Barry M, Curtin K, Beausang E, Barry R, Coyne I. Neoadjuvant treatment for stage III and IV cutaneous melanoma. Cochrane Database Syst Rev. 2023 Jan 17;1(1):CD012974. doi: 10.1002/14651858.CD012974.pub2.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katharina C. Kähler, MD principal investigator
University Hospital Schleswig-Holstein
Mario Santinami, MD principal investigator
Istituto Nazionale Tumori Milano
Piotr Rutkowski, MD principal investigator
Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie Warszawa
22 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing L19IL2 + L19TNF and Surgery in people with Malignant Melanoma, run by Philogen S.p.A. at 22 sites in 4 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 20 inclusion and 22 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: under way, not looking for participants, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in Germany, Italy, France, Poland. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence-free survival (RFS) rate (time frame: 1 year after randomization). 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 NCT02938299, which also lists 3 linked publications.
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 19 Sep 2024.