Melanoma Stage IIIB-IVPhase 2NeoLIPANCT06651151
NeoLIPA: Neoadjuvant LTX-315 in Combination with Pembrolizumab in Resectable Stage III/IV Melanoma
A Phase 2 study testing LTX-315 + pembrolizumab in people with Melanoma Stage IIIB-IV, run by Oslo University Hospital at 1 site in Norway.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma Stage IIIB-IV
- What is being tested?
- LTX-315 + pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteNorway
- Study dates
- 1 Nov 2024to May 2031
- Phase
- Phase 2
- 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
- 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.
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- 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
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: 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 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.
Read more
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.
Read the detailed 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.
- Conditions
- Melanoma Stage IIIB-IV
- Being tested
- LTX-315 + pembrolizumab
- Keywords
- Melanoma, Neoadjuvant, Pembrolizumab, Oncolytic peptide
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LTX-315 + pembrolizumabDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: LTX-315 + pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Pathologic Response Rate
Rate of pathologic complete response (pCR), defined as complete absence of viable tumor in the treated tumor bed.
Measured: 12 weeks after start of treatment
Secondary outcomes (7)
Safety Evaluation
Frequency, nature and severity of AE according to NCI CTCAE v 5.0:
- All AEs
- LTX-315 treatment-related AEs
- LTX-315 and/or pembrolizumab treatment-related AEs
Measured: Continously from first dose of treatment to 90 days after last study drug administration
Objective response rate (ORR)
Rate of CR or PR as per RECIST version 1.1 prior to surgery
Measured: After 12 weeks of treatment
Pathologic Response Rate
Rate of partial (less than 50% of the treated tumor bed is occupied by viable tumor cell) or complete pathologic response.
Rate of Major Pathologic Response (MPR) defined as complete or near-complete (less than 10% of viable tumor in the treated tumor bed) pathologic response
Measured: After 12 weeks of treatment
Event free survival (EFS)
Defined as time from start of treatment to progression of disease that precludes surgery, recurrence (local or distant) or death
Measured: From first dose of treatment to two years
Recurrence free survival (RFS)
Defined as the time from surgery to recurrence or death.
Measured: Two years after surgery
Overall Survival (OS)
Overall Survival
Measured: Three years after surgery
Quality of Life (QoL)
Patient reported outcomes (PRO)
Measured: From first dose to end of treatment at approximately 1.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2024
- Study start1 Nov 2024 (estimated)
- Primary completionMay 2026 (estimated)
- Study completionMay 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Melanoma Stage IIIB-IVStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Lytix Biopharma AS
- Responsible party
- Principal investigator, Henrik Jespersen, Oslo University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06651151
- Sponsor's protocol ID
- 2023_16
- Other IDs
- 2023-508649-42-00, 2023
- Acronym
- NeoLIPA
- Status last verified
- Oct 2024
- First submitted
- 18 Oct 2024
- Last updated
- 26 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06651151
- Acronym / sponsor ID
- NeoLIPA / 2023_16
- Conditions
- Melanoma Stage IIIB-IV
- Keywords
- Melanoma, Neoadjuvant, Pembrolizumab, Oncolytic peptide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- Lytix Biopharma AS
- Study start
- 1 Nov 2024 (estimated)
- Primary completion
- May 2026 (estimated)
- Study completion
- May 2031 (estimated)
- First posted
- 21 Oct 2024 (actual)
- 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.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: LTX-315 + pembrolizumabLTX-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (15 listed)
- 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.
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 |
|---|---|---|
| LTX-315 + pembrolizumabLTX-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 | Drug | Experimental |
Primary outcome
Complete Pathologic Response Rate
Time frame: 12 weeks after start of treatment
Rate of pathologic complete response (pCR), defined as complete absence of viable tumor in the treated tumor bed.
7 secondary outcomes
Safety Evaluation
Time frame: Continously from first dose of treatment to 90 days after last study drug administration
Objective response rate (ORR)
Time frame: After 12 weeks of treatment
Pathologic Response Rate
Time frame: After 12 weeks of treatment
Event free survival (EFS)
Time frame: From first dose of treatment to two years
Recurrence free survival (RFS)
Time frame: Two years after surgery
Overall Survival (OS)
Time frame: Three years after surgery
Quality of Life (QoL)
Time frame: From first dose to end of treatment at approximately 1.5 years
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 26 Oct 2024.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LTX-315 + pembrolizumab in people with Melanoma Stage IIIB-IV, run by Oslo University Hospital at 1 site in Norway.
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 14 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 26 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Henrik Jespersen, MD PhD (0047 22187285, hejes@ous-hf.no), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete Pathologic Response Rate (time frame: 12 weeks after start of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 26 Oct 2024.