NeoLIPA: Neoadjuvant LTX-315 in Combination with Pembrolizumab in Resectable Stage III/IV Melanoma

NCT06651151 | Recruiting Phase 2

• 2 other identifiers: 2023_162023-508649-42-00
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial aims to evaluate the effectiveness of a new treatment approach for patients with stage III or IV melanoma that has spread to other parts of the body but can still be surgically removed. The study combines two treatments: LTX-315 and pembrolizumab. Melanoma that has spread to other parts of the body can often be treated with surgery. Despite surgery, there is a high risk of the cancer coming back. Pembrolizumab, an immune checkpoint inhibitor, can reduce this risk when given after surgery. Recent studies have shown that giving pembrolizumab before surgery, along with post-surgery treatment, might be more effective than giving it only after surgery. However, many patients still experience cancer recurrence. Combining pembrolizumab with LTX-315, which triggers a different immune response, might improve the treatment\'s effectiveness and reduce the risk of cancer progression before surgery. This is an open-label Phase II study, meaning both the researchers and participants will know which treatments are being given. The study will be conducted at a single center and will involve about 27 participants. They will receive LTX-315 and pembrolizumab before their planned surgery to see if this combination could be more effective than pembrolizumab alone. The primary goal is to assess the tumors response to the neoadjuvant (pre-surgery) treatment, specifically looking at the rate of pathological complete response (pCR), where no cancer is detected in the removed tumor tissue.

Conditions

Melanoma Stage IIIB-IV

Keywords

Melanoma; Neoadjuvant; Pembrolizumab; Oncolytic peptide

Outcome Measures

Primary Outcomes (1)

• Complete Pathologic Response Rate

  Rate of pathologic complete response (pCR), defined as complete absence of viable tumor in the treated tumor bed.

  12 weeks after start of treatment

Secondary Outcomes (7)

• Safety Evaluation

  Continously from first dose of treatment to 90 days after last study drug administration

• Objective response rate (ORR)

  After 12 weeks of treatment

• Pathologic Response Rate

  After 12 weeks of treatment

• Event free survival (EFS)

  From first dose of treatment to two years

• Recurrence free survival (RFS)

  Two years after surgery

Study Arms (1)

Experimental

EXPERIMENTAL

LTX-315 will be injected directly into the selected tumor once weekly for a maximum of 5 dosing days. Pembrolizumab will be given as 200 mg IV infusion over 30 minutes every 3 weeks for a maximum of 18 doses of which three doses will be given prior to the planned surgery.

Drug: LTX-315 + pembrolizumab

Interventions

LTX-315 + pembrolizumab DRUG

LTX-315 as intratumoral injection once weekly for a maximum of 5 dosing days, in combination with pembrolizumab as intravenous infusion, 200 mg every 3 weeks for a maximum of 18 doses

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Hemoglobin \> 9 g/dL
• Absolute neutrophil count (ANC) ≥ 1.0 x 109/L
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Oslo University Hospital: lead
• Lytix Biopharma AS: collaborator

Study Sites (1)

Oslo University Hospital

Oslo, Oslo County, 0491, Norway

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

LTX-315; pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Henrik Jespersen, MD PhD

CONTACT

0047 22187285; hejes@ous-hf.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Melanoma Oncology, Group Leader Melanoma Research

Study Record Dates

• First Submitted: October 18, 2024
• First Posted: October 21, 2024
• Study Start: November 1, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): May 1, 2031
• Last Updated: October 26, 2024

Record last verified: 2024-10

Locations

NO (1)