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

Last updated: October 23, 2024
Sponsor: Oslo University Hospital
Overall Status: Active - Recruiting

Phase

2

Condition

Melanoma

Treatment

LTX-315 + pembrolizumab

Clinical Study ID

NCT06651151
2023_16
2023-508649-42-00
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Participant must be 18 years of age inclusive, at the time of signing the informedconsent.

  • Histologically confirmed, clinically detectable stage III-IV(M1a) melanoma, judgedfully resectable and eligible for neoadjuvant treatment by consensus at amultidisciplinary tumor board. Patients with melanoma of cutaneous (including acral)or mucosal (including conjunctival) origin are eligible. Clinically detectable isdefined as being apparent and measurable by radiological assessments or physicalexamination.

  • 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 availablefor injection with a maximum mean longest perpendicular diameter (LPD) of 3.0 cm.

  • Willing to undergo an additional tumor biopsy and submit biopsy and surgicalspecimens

  • 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 measuredcreatinine clearance (CL) >30 mL/min

  • Female participants are willing to use contraceptive measures as prescribed by theprotocol 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 testwithin 72 hours of first study intervention.

  • Capable of giving signed informed consent as described in section 10.1 whichincludes compliance with the requirements and restrictions listed in the informedconsent form (ICF) and in this protocol.

Exclusion

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 abnormalitythat might confound the results of the trial, interfere with the subject'sparticipation for the full duration of the trial, or is not in the best interest ofthe subject to participate, in the opinion of the treating Investigator.

  • Active autoimmune disease requiring systemic immunomodulatory treatment. Replacementtherapy (e.g. physiologic doses of corticosteroids, insulin, thyroxine) is allowed.

  • Patient has history of, or any evidence of interstitial lung disease (ILD) ornon-infectious pneumonitis that required systemic corticosteroids.

  • Prior malignancy that require concurrent therapy.

  • Allergy/hypersensitivity to prophylactic treatments; known hypersensitivity topembrolizumab 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 mgof prednisolone or equivalent) or other systemic immunosuppressive drugs within 28days prior to study drug administration. Topical and inhaled corticosteroids areallowed.

  • 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 toreceive one during the treatment period.

  • Pregnant or breastfeeding.

  • Any reason why, in the opinion of the investigator, the patient should notparticipate.

Study Design

Total Participants: 27
Treatment Group(s): 1
Primary Treatment: LTX-315 + pembrolizumab
Phase: 2
Study Start date:
November 01, 2024
Estimated Completion Date:
May 31, 2031

Study Description

This is a single arm, single center, open-label phase II study to assess the effect of neoadjuvant LTX-315 in combination with pembrolizumab in patients with clinically detectable and resectable stage III-IV melanoma.

Clinically detectable, fully resectable stage III or oligometastatic IV melanoma can be cured with surgery but has a very high risk of local or systemic recurrence. The risk of recurrence can be significantly reduced by adjuvant treatment with a PD-1 inhibitor. Due to the mode of action of PD-1 inhibitors (stimulating tumor reactive T cells), there is reason to believe that their effect is enhanced if given before definitive surgery and removal of tumor reactive T cells in the tumor microenvironment. Indeed, it was recently shown that the effect is greatly improved if three doses of pembrolizumab are administered prior to surgery (neoadjuvant), followed by 15 doses in the adjuvant setting, compared to giving 18 doses adjuvant.

Several studies have shown that pathologic complete response (pCR) after neoadjuvant treatment correlates with recurrence-free survival (RFS). The pCR rate neoadjuvant pembrolizumab is only modest (20%), and for 8% of the patients, disease progression in the neoadjuvant phase precludes the planned surgery.

LTX-315 is an oncolytic peptide generated from a host defense peptide and has both a direct killing activity and immunomodulatory properties. By inducing cell lysis and immunogenic cell death, LTX-315 can lead to increased T-cell infiltration, broadened repertoire of tumor antigens and increased diversity of T-cell clones, and thus has the potential to enhance the effect of pembrolizumab. Furthermore, the addition of LTX-315 to neoadjuvant pembrolizumab can lower risk of disease progression precluding surgery.

Connect with a study center

  • Oslo University Hospital

    Oslo, 0491
    Norway

    Active - Recruiting

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