Informations générales (source: ClinicalTrials.gov)
Randomized, Ph3 Clinical Study Comparing Vusolimogene Oderparepvec in Combination With Nivolumab Vs Treatment of Physician's Choice in Patients With Advanced Melanoma That Progressed on Anti-PD-1 and Anti-CTLA-4 Containing Treatment [IGNYTE-3]
Interventional
Phase 3
Replimune Inc. (Voir sur ClinicalTrials)
juillet 2024
août 2034
02 avril 2026
This is a randomized, controlled, multicenter, open-label Phase 3 clinical study
comparing VO in combination with nivolumab versus Physician's Choice treatment for
patients with unresectable Stage IIIb-IV cutaneous melanoma whose disease progressed on
an anti PD-1 and an anti-CTLA-4 containing regimen (administered either as a combination
regimen or in sequence) or who are not candidates for treatment with an anti-CTLA-4
therapy.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Caroline ROBERT | 20/04/2026 16:00:07 | Contacter | ||
Critères
Tous
I 1. Male or female who is 12 years of age or older at the time of signed informed
consent.
I 2. Patients with histologically or cytologically confirmed unresectable or metastatic
Stage IIIb through IV/M1a through M1d cutaneous melanoma, as per AJCC staging system, 8th
edition).
I 3. Confirmed disease progression (PD) on an anti-PD-1 antibody treatment and an
anti-CTLA-4 antibody treatment, administered as either a combination regimen (eg,
nivolumab + ipilimumab) or in sequence.
1. Treatment with prior anti-PD-1 therapy must have continued for a minimum of 8 weeks
(note: treatment with prior pembrolizumab therapy when administered every 6 weeks
must have continued for a minimum of 12 weeks [ie, 2 treatment cycles]). Any number
of doses of prior anti-CTLA-4 therapy may have been administered in combination with
an anti-PD-1. The anti-PD-1-containing therapy must be the immediate prior line of
treatment before randomization (for patients with BRAF mutation, see I 4).
2. Patients who in the physician's judgement are not candidates for treatment with an
anti-CTLA-4 antibody (eg, due to documented clinically significant comorbidities or
history of immune-related adverse events) are eligible for the study if they have
confirmed PD on an anti-PD-1 antibody (including unresectable disease relapse during
adjuvant therapy or < 6 months from completion of adjuvant therapy).
3. Disease progression must have been confirmed and documented using clinical or
radiological assessment by 2 assessments at least 4 weeks apart while being treated
with an anti-PD-1 antibody and an anti-CTLA-4 antibody. Radiological confirmation of
PD can occur during the Screening period for this study. Treatment with prior
anti-PD-1 therapy must have continued from the time of initial tumor progression
until confirmation of PD (ie, such that no doses of anti-PD-1 therapy were missed).
Note: If radiographic progression at the initial scan where PD was documented is
accompanied by clear clinical progression, defined as a decline in performance status
directly attributed to disease or increased disease-related symptoms, anti-PD-1 therapy
does not need to continue. For patients with documented PD while on adjuvant therapy with
an anti-PD-1 therapy, a confirmatory biopsy can be used in place of a confirmatory scan.
I 4. Has documented BRAF V600 mutation status or must consent to BRAF V600 mutation
testing per local institutional standards during the Screening period. Patients with BRAF
mutation should have received prior BRAF-directed therapy (with or without a MEK
inhibitor) prior to randomization, unless deemed not clinically indicated at
Investigator's discretion due to concurrent medical condition or prior toxicity.
Note: Prior exposure to BRAF-directed therapy (with or without a MEK inhibitor) includes
treatment in the adjuvant setting. One line of BRAF-directed therapy (with or without a
MEK inhibitor) can be the most recent systemic treatment administered before
randomization.
I 5. Has least 1 measurable tumor of ≥ 1 cm in longest diameter (or shortest diameter for
lymph nodes) and injectable lesion(s) of at least 1 cm in longest diameter.
I 6. Has adequate hematologic function, including:
1. White blood cell (WBC) count ≥ 2.0 × 109/L
2. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
3. Platelet count ≥ 75 × 109/L
4. Hemoglobin ≥ 8 g/dL (without packed red blood cell [RBC] transfusion within 2 weeks
of dosing)
I 7. Has adequate hepatic function, including:
1. Total bilirubin ≤ 1.5 × upper limit of normal (ULN; < 2.0 × ULN for patients with
known Gilbert syndrome or liver metastases)
2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3.0 × ULN (or ≤
5.0 × ULN, if liver metastases are present)
3. Alkaline phosphatase (ALP) ≤ 2.5 × ULN (or ≤ 5.0 × ULN, if liver or bone metastases
are present) I 8. Has adequate renal function, defined as serum creatinine ≤ 1.5 ×
ULN or creatinine clearance ≥ 3 0 mL/minute/1.73 m2 (measured using Chronic Kidney
Disease Epidemiology Collaboration [CKD-EPI] formula).
I 9. Prothrombin time (PT) ≤ 1.5 × ULN (or international normalization ratio [INR] ≤ 1.3)
and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤
1.5 × ULN. Note: Patients who are on chronic anticoagulant therapy may be randomized if
the target INR is ≤ 2.5. For patients requiring deep injection of VO, the INR must be
<1.5 at the time of injection.
I 10. ECOG performance status (PS) 0 to 1 for patients 18 and older or a Lansky PS ≥ 80
for patients 12 to 17 years of age.
I 11. Life expectancy of at least 3 months. I 12. Female and male patients of
reproductive potential must agree to avoid becoming pregnant or impregnating a partner
and adhere to highly effective contraception requirements during the treatment period and
for at least 6 months after the last dose of any study treatment.
I 13. Women of childbearing potential must have a negative serum beta-human chorionic
gonadotropin (β-hCG) test with a minimum sensitivity of 25 IU/L or equivalent units or β
hCG within 7 days before the first dose of study treatment.
I 14. Capable of giving signed informed consent which includes willingness to comply with
the requirements and restrictions listed in the informed consent form (ICF)
Key Exclusion Criteria:
E 1. Primary mucosal or uveal melanoma. E 2. More than 2 lines of systemic therapy for
advanced melanoma. Note: One additional line of anti-PD-1 therapy in the adjuvant or
neoadjuvant setting is allowed if the patient was free of treatment and of PD for at
least 6 months and subsequently had confirmed PD on an anti-PD-1 and an anti-CTLA-4
antibody therapy administered in the advanced setting.
E 3. Known acute or chronic hepatitis B (defined as hepatitis B surface antigen [HBsAg]
reactive) or known acute or chronic hepatitis C virus (defined as HCV RNA [qualitative]
is detected).
Note: Patients who have been effectively treated are eligible for randomization. Patients
must be negative for HBsAg and HCV RNA.
E 4. Known human immunodeficiency virus (HIV) infection. Note: Testing for HIV is not
required unless mandated by local health authority or clinically indicated.
E 5. Active significant herpetic infections or prior complications of HSV-1 infection
(eg, herpetic keratitis or encephalitis) or requires intermittent or chronic use of
systemic (oral or IV) antivirals with known antiherpetic activity (eg, acyclovir).
Note: Patients with sporadic cold sores may be randomized if no active cold sores are
present at the time of first dose of study treatment.
E 6. Had systemic infection requiring IV antibiotics or other serious active infection
requiring antimicrobial, antiviral, or antifungal treatment within 14 days prior to the
first dose.
E 7. Evidence of spinal cord compression or at high risk of spinal cord compression.
E 8. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
at time of screening. Patients with known central nervous system metastases are eligible
if they have received standard-of-care therapy for central nervous system disease (such
as stereotactic radiosurgery or radical surgical resection followed by radiotherapy) and
have evidence of disease stability on 2 subsequent scans performed at least at a 4-week
interval.
E 9. Serum lactate dehydrogenase (LDH) > 2 × ULN. E 10. Major surgery ≤ 2 weeks prior to
starting study treatment. Note: Patients must have recovered adequately from all acute
complications of all previous procedures prior to randomization.
E 11. Prior malignancy active within the previous 3 years, except for locally curable
cancers that have apparently been cured, such as basal or squamous cell skin cancer,
superficial bladder cancer, or carcinoma in situ (without invasive component) of the
prostate, cervix, or breast.
E 12. History of significant cardiac disease including myocarditis or congestive heart
failure (defined as New York Heart Association Functional Classification III or IV), or
unstable angina, serious uncontrolled cardiac arrhythmia, cerebral vascular accident, or
myocardial infarction within 6 months from first dose of VO.
E 13. History of life-threatening toxicity related to prior immune therapy except those
that are unlikely to recur with standard countermeasures (eg, hormone replacement after
adrenal crisis).
E 14. History or evidence of psychiatric, substance abuse (including IV substance abuse),
or any other clinically significant disorder, condition, or disease (with the exception
of those described above) that, in the opinion of the Investigator or the Medical
Monitor, would pose a risk to patient safety or interfere with the study evaluation,
procedures, or completion.
E 15. History or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the patient's participation
for the full duration of the study, or is not in the best interest of the patient to
participate, in the opinion of the treating Investigator.
E 16. Active, known, or suspected autoimmune disease requiring systemic treatment.
E 17. History of (noninfectious) pneumonitis that required steroids or has current
pneumonitis.
E 18. Prior oncolytic virus therapy or other therapy given by intratumoral
administration.
E 19. Requires chronic use of systemic (oral or IV) antivirals with known antiherpetic
activity (eg, acyclovir).
E 20. Has received a live vaccine within 28 days prior to the first dose of study
treatment.
E 21. Systemic anticancer therapies within 5 half-lives or 4 weeks of the first dose,
whichever is shorter.
E 22. Is currently participating in or has participated in a study of an investigational
agent within 4 weeks prior to the first dose of study treatment.
E 23. Has received prior radiotherapy within 2 weeks of start of study treatment or has
not recovered from radiotherapy.
E 24. Conditions requiring treatment with immunosuppressive doses (> 10 mg per day of
prednisone or equivalent) of systemic corticosteroids other than for corticosteroid
replacement therapy 14 days before randomization.
Note: Patients who require a brief course (≤ 7 days) or corticosteroids (eg, as
prophylaxis for imaging studies due to hypersensitivity to contrast agents) are not
excluded. Physiologic replacement doses of systemic corticosteroids are permitted, only
if the dose does not exceed 10 mg/day prednisone equivalent.
E 25. History of allergy or sensitivity to study drug components (VO, nivolumab,
pembrolizumab, or relatlimab) or to cisplatin or carboplatin or paclitaxel (dependent on
cohort) or prior monoclonal antibody treatment.
E 26. Treatment with botanical preparations (eg, herbal supplements or traditional
Chinese medicines) intended for general health support or to treat the disease under
study within 2 weeks prior to treatment.
E 27. Is a person who is deprived of freedom by an administrative or court order, or in
an emergency setting, or hospitalized involuntarily.