NeoLIPA: Neoadjuvant LTX-315 in combination with pembrolizumab in resectable stage III/IV melanoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

23 Oct 2024 → ongoing

Decision date (initial)

2024-04-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Lytix Biopharma AS

External identifiers

EU CT number

2023-508649-42-00

WHO UTN

U1111-1301-9659

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Tumor response of neoadjuvant treatment. Meassured by rate of pathological response (pCR)

Secondary objectives 4

1. Safety evaluation.
2. Tumor response of neoadjuvant treatment.
3. Clinical response
4. Quality of life

Conditions and MedDRA coding

Patients with clinically detectable and resectable stage III-IV melanoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Participant must be 18 years of age inclusive, at the time of signing the informed consent.
2. 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
3. Measurable disease as per RECIST version 1.1 criteria.
4. Judged medically fit to undergo the planned surgery by the surgical team.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Have at least one superficial cutaneous, subcutaneous or lymph node lesion available for injection with a maximum mean longest perpendicular diameter (LPD) of 5.0 cm.
7. Willing to undergo an additional tumor biopsy and submit biopsy and surgical specimens
8. Adequate organ function as defined below: a. Hemoglobin > 9 g/dL b. Absolute neutrophil count (ANC) ≥ 1.0 x 109/L c. 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
9. Capable of giving signed informed consent.

Exclusion criteria 14

1. Uveal melanoma. Patients with acral, mucosal or conjunctival melanoma are eligible.
2. History of brain, bone, liver metastases or leptomeningeal metastases.
3. Patients with stage IV disease having ≥4 metastatic sites.
4. 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.
5. Active autoimmune disease requiring systemic immunomodulatory treatment. Replacement therapy (e.g. physiologic doses of corticosteroids, insulin, thyroxine) is allowed.
6. Patient has history of, or any evidence of interstitial lung disease (ILD) or non-infectious pneumonitis that required systemic corticosteroids.
7. Prior malignancy that require concurrent therapy.
8. Allergy/hypersensitivity to prophylactic treatments; known hypersensitivity to pembrolizumab or LTX-315 or any of their excipients
9. 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).
10. 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.
11. Have received a live vaccine within 30 days prior to first dose of treatment
12. Have received an investigational drug within 4 weeks to day 1, or are scheduled to receive one during the treatment period
13. Pregnant or breastfeeding.
14. Any reason why, in the opinion of the investigator, the patient should not participate.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rate of pathologic complete response (cPR)

Secondary endpoints 4

1. Frequency, nature and severity of AE according to NCI CTCAE v 5.0: • All AEs • LTX-315 treatment-related AEs • Pembrolizumab treatment-related AEs The proportion of patients who received surgery as planned Number of doses of LTX-315 and pembrolizumab recieved
2. Objective response rate (ORR), i.e. rate of CR or PR as per RECIST version 1.1 prior to surgery Pathologic response rate (pCR + pPR) Rate of major pathologic response (MPR) defined as pCR and pnCR
3. Event free survival (EFS), defined as time from start of treatment to progression of disease per RECIST version 1.1 that precludes surgery, recurrence (local or distant) or death. Recurrence free survival (RFS), defined as the time from surgery to recurrence or death. Overall Survival (OS)
4. Patient reported outcomes (PRO)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital HF

Sponsor organisation

Oslo University Hospital HF

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital HF

Contact name

Henrik Jespersen

Public contact point

Organisation

Oslo University Hospital HF

Contact name

Henrik Jespersen

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications