Combining LTX-315 and pembrolizumab for treating advanced melanoma before surgery

NeoLIPA: a Single Center Phase II Open Label Study of Neoadjuvant LTX-315 in Combination with Pembrolizumab in Patients with Clinically Detectable and Resectable Stage III-IV Melanoma

This study is testing a new treatment that combines LTX-315 and pembrolizumab to see if it helps people with advanced melanoma do better after surgery.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Oslo University Hospital (other)
• Drugs / interventions: pembrolizumab, trametinib, immunotherapy
• Locations: 1 site (Oslo, Oslo)
• Trial ID: NCT06651151 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of a new treatment approach for patients with stage III or IV melanoma that can still be surgically removed. It combines LTX-315, an oncolytic peptide, with pembrolizumab, an immune checkpoint inhibitor, administered before surgery to enhance the immune response against the cancer. The study aims to determine if this combination can improve outcomes and reduce the risk of cancer recurrence compared to standard treatment. It is an open-label Phase II study conducted at a single center.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with clinically detectable, fully resectable stage III-IV melanoma.

Not a fit: Patients with melanoma that is not resectable or those with other severe health conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of melanoma recurrence after surgery.

How similar studies have performed: Previous studies have shown promise with neoadjuvant pembrolizumab, but the combination with LTX-315 is a novel approach.

Eligibility criteria

Inclusion Criteria:

* Participant must be 18 years of age inclusive, at the time of signing the informed consent.
* Histologically confirmed, clinically detectable stage III-IV(M1a) melanoma, judged fully resectable and eligible for neoadjuvant treatment by consensus at a multidisciplinary tumor board. Patients with melanoma of cutaneous (including acral) or mucosal (including conjunctival) origin are eligible. Clinically detectable is defined as being apparent and measurable by radiological assessments or physical examination.
* Measurable disease as per RECIST version 1.1 criteria.
* Judged medically fit to undergo the planned surgery by the surgical team.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Have at least one superficial cutaneous, subcutaneous or lymph node lesion available for injection with a maximum mean longest perpendicular diameter (LPD) of 3.0 cm.
* Willing to undergo an additional tumor biopsy and submit biopsy and surgical specimens
* Adequate organ function as defined below:

  1. Hemoglobin \> 9 g/dL
  2. Absolute neutrophil count (ANC) ≥ 1.0 x 109/L
  3. Platelet count ≥ 80 x 109/L

  e. Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) f. AST and ALT ≤2.5 x ULN g. Albumin \>30 g/L h. Serum creatinine ≤1.5 X ULN OR measured creatinine clearance (CL) \>30 mL/min
* Female participants are willing to use contraceptive measures as prescribed by the protocol from study visit 1 to 120 days after the last dose of study intervention. Women of childbearing potential must have a negative urine or serum pregnancy test within 72 hours of first study intervention.
* Capable of giving signed informed consent as described in section 10.1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

* Uveal melanoma. Patients with acral, mucosal or conjunctival melanoma are eligible.
* History of brain, bone, liver metastases or leptomeningeal metastases.
* Patients with stage IV disease having ≥4 metastatic sites.
* A history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
* Active autoimmune disease requiring systemic immunomodulatory treatment. Replacement therapy (e.g. physiologic doses of corticosteroids, insulin, thyroxine) is allowed.
* Patient has history of, or any evidence of interstitial lung disease (ILD) or non-infectious pneumonitis that required systemic corticosteroids.
* Prior malignancy that require concurrent therapy.
* Allergy/hypersensitivity to prophylactic treatments; known hypersensitivity to pembrolizumab or LTX-315 or any of their excipients
* Previous treatment with anti-cancer immunotherapy, including (but not limited to) CTLA-4 or PD-1 inhibitors. Prior non-immunotherapy adjuvant treatment (e.g.

dabrafenib + trametinib or radiotherapy), and regional therapy such as ECT or ILP is permitted (≥ 12 weeks prior to enrollment).

* Currently taking immunosuppressive agents or use of systemic corticosteroids (≥10 mg of prednisolone or equivalent) or other systemic immunosuppressive drugs within 28 days prior to study drug administration. Topical and inhaled corticosteroids are allowed.
* Have received a live vaccine within 30 days prior to first dose of treatment
* Have received an investigational drug within 4 weeks to day 1, or are scheduled to receive one during the treatment period.
* Pregnant or breastfeeding.
* Any reason why, in the opinion of the investigator, the patient should not participate.

Where this trial is running

Oslo, Oslo

• Oslo University Hospital — Oslo, Oslo, Norway (RECRUITING)

Study contacts

• Study coordinator: Henrik Jespersen, MD PhD

Conditions: Melanoma Stage IIIB-IV, Melanoma, Neoadjuvant, Pembrolizumab, Oncolytic peptide