Phase 3 Randomized Study of IO102-IO103 and Pembrolizumab Versus Pembrolizumab Monotherapy in Untreated Unresectable or Metastatic Melanoma
- Trial ID
- 2024-511996-13-00
- Protocol
- IOB-013/KN-D18
- Sponsor
- Io Biotech ApS
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 3 clinical trial is to evaluate the **efficacy** of IO102-IO103 in combination with **pembrolizumab** compared to pembrolizumab alone in patients with previously untreated, unresectable, or metastatic melanoma. The primary endpoint is progression-free survival (PFS), which is a critical measure of how long patients live without the disease worsening. This is clinically relevant as it provides insight into the potential of the combination therapy to delay disease progression in advanced melanoma, a condition with limited treatment options.
Secondary objectives include further exploration of the efficacy of IO102-IO103 in combination with pembrolizumab compared to pembrolizumab alone in terms of overall response rate (ORR), overall survival (OS), durable response rate (DRR), and complete remission rate (CRR). Additionally, the study aims to investigate the safety and tolerability of the treatment. These secondary endpoints are important for understanding the broader impact of the treatment on patient outcomes and its safety profile, which are essential for determining the overall benefit-risk ratio of the therapy.
Participants
The clinical trial involves a total of **80 participants** diagnosed with **previously untreated, unresectable, or metastatic melanoma**. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants were selected based on specific inclusion criteria, such as having a histologically or cytologically confirmed stage III (unresectable) or stage IV melanoma, being treatment-naive, and possessing an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. The trial does not specify particular lifestyle considerations such as diet or physical activity. The population includes vulnerable groups, ensuring a comprehensive assessment of the investigational treatment's efficacy. The trial aims to evaluate the efficacy of IO102-IO103 in combination with pembrolizumab compared to pembrolizumab alone, focusing on progression-free survival.
Plans and Procedures
The clinical trial is designed as an open-label, randomized, Phase 3 study to evaluate the efficacy of **IO102-IO103** in combination with **pembrolizumab** compared to pembrolizumab alone in patients with previously untreated, unresectable, or metastatic melanoma. The primary objective is to assess progression-free survival (PFS), with secondary endpoints including overall response rate (ORR) and overall survival (OS). The trial is expected to run from December 2020 to August 2027, with a maximum treatment period of 24 months for participants.
Participants will be randomly assigned to receive either the combination therapy or pembrolizumab alone. The study involves multiple visits, starting with a screening visit to confirm eligibility based on criteria such as histologically confirmed stage III or IV melanoma, treatment-naive status, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Following randomization, participants will undergo regular follow-up visits to monitor treatment response and safety, with assessments conducted according to RECIST v1.1 criteria. The end-of-study visit will occur after the completion of the treatment period or upon early termination.
Participant involvement is expected to last up to 24 months, with conditions for early termination including disease progression, unacceptable toxicity, or withdrawal of consent. The trial will ensure rigorous monitoring and data collection to evaluate the therapeutic potential of the investigational combination therapy in this patient population.
Treatment
The clinical trial involves the administration of **KEYTRUDA** (pembrolizumab), a **concentrate for solution for infusion**. This experimental medication is provided in a concentration of 25 mg/mL and is administered via **intravenous use**. The maximum daily dose is 200 mg, with a total maximum dose of 7000 mg over a treatment period of up to 24 months. Pembrolizumab is a protein-based therapeutic agent, specifically classified under the ATC code L01FF02. The product is manufactured by Merck Sharp & Dohme B.V. and holds the marketing authorization number EU/1/15/1024/002. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol.
Another experimental treatment in the trial is **IO102-IO103**, a **lyophilized powder for preparation for injection**. This medication is administered via **subcutaneous injection**. The maximum daily dose is 170 µg, with a total maximum dose of 6.29 mg over a 24-month treatment period. IO102-IO103 is combined with Montanide ISA 51 VG, a sterile emulsion for injection, to enhance its therapeutic efficacy. The active substance, IO103 acetate, is also a protein-based agent. This product is developed by IO Biotech APS and is identified by the sponsor product code IO102-IO103. Participant compliance with the administration schedule is closely monitored to ensure the integrity of the trial results.
Efficacy
The efficacy of the investigational treatment in this Phase 3 clinical trial will be assessed primarily through **Progression-Free Survival (PFS)**. PFS is defined as the time from randomization to the first documented disease progression or death from any cause, as determined by an Independent Review Committee (IRC) in accordance with RECIST v1.1 criteria. Patients who have not experienced disease progression or death at the time of analysis will be censored at the date of their last disease assessment.
Secondary efficacy endpoints include the **Overall Response Rate (ORR)** and **Overall Survival (OS)**. ORR is defined as the percentage of patients achieving a confirmed partial response or complete response, as evaluated by the IRC using RECIST v1.1 criteria. OS is defined as the time from randomization until death from any cause, with patients not known to have died being censored at the date they were last known to be alive.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Histologically or cytologically confirmed stage III (unresectable) or stage IV melanoma, as per American Joint Committee on Cancer 8th edition guidelines not amenable to local therapy (90). 2. Patients are treatment naive—that is, no previous systemic anticancer therapy for unresectable or metastatic melanoma. For clarification, the following patients are eligible: a. Patients with BRAFV600 mutation-positive melanoma are eligible if treatment naive and without rapidly progressive disease as per investigators assessment.D ocumented BRAFV600 mutation status must be available from all patients prior to trial entry. b. Patients who have received previous adjuvant and/or neoadjuvant therapy with targeted therapy or immune therapy are eligible if administered the last dose at least 6 months before inclusion and if relapse did not occur during active treatment or within 6 months of treatment discontinuation. 3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 0 or 1 assessed within 10 days before randomization. 4. Life expectancy of >24 weeks at the time of informed consent per investigator assessment. 5. At least 1 measurable lesion according to response evaluation criteria for solid tumors (RECIST v1.1) and confirmed by IRC. Note: Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions before inclusion. 6. Provision of archival (obtained within 3 months) or newly acquired biopsy tissue not previously irradiated, and blood at screening for biomarker assessments. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. Note: • Use of archival tissue >3 months old, may be considered after communication with and agreement by the Sponsor. • If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut (details pertaining to tumor tissue submission can be found in the Lab Manual). For the full list of inclusion criteria, please refer to the protocol.
Exclusion Criteria
- Uveal/ocular, acral or mucosal melanoma 2. Patients with known or suspected central nervous system (CNS) metastases or with the CNS as the only site of active disease are excluded with the following exception: Patients with controlled (stable) brain metastases will be allowed to enroll (subject to baseline magnetic resonance imaging confirmation). Controlled (stable) brain metastases are defined as those with no radiographic progression for at least 4 weeks after radiation and/or surgical treatment at the time of signed informed consent. Patients must have been off steroids for at least 2 weeks before signed informed consent and have no new or progressive neurological signs and symptoms. 3. Patient has received previous radiotherapy within 2 weeks of start of trial treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease. 4. Patients with BRAFV600-positive disease who are experiencing rapidly progressing disease and/or have received standard first-line therapy with BRAF and/or MEK inhibitor for unresectable or metastatic disease. 5. Active known or suspected autoimmune disease that has required systemic treatment in the past 2 years. Patients with type I diabetes mellitus; hypothyroidism only requiring hormone replacement; skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment; or conditions not expected to recur in the absence of an external trigger are permitted to enroll. 6. Presence of other primary malignancies, with the exception of non-melanoma skin cancer, carcinoma in situ or stage I nonulcerative melanoma, in situ cervical cancer, in situ breast cancer and prostate cancer for patients who are receiving androgen deprivation therapy only. Other primary malignancies are only acceptable if there is no ongoing active disease and no biomarker indication of active disease. 7. Active infection requiring systemic therapy 8. History of active tuberculosis For the full list of exclusion criteria, please refer to the protocol.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 30 Dec 2020 | 3 |
 Czechia | Not Recruiting | 30 Dec 2020 | 9 |
 Denmark | Not Recruiting | 30 Dec 2020 | 22 |
 France | Not Recruiting | 30 Dec 2020 | 79 |
 Germany | Not Recruiting | 30 Dec 2020 | 94 |
 Hungary | Not Recruiting | 30 Dec 2020 | 8 |
 Italy | Not Recruiting | 30 Dec 2020 | 40 |
 The Netherlands | Not Recruiting | 30 Dec 2020 | — |
 Poland | Not Recruiting | 30 Dec 2020 | 16 |
 Spain | Not Recruiting | 30 Dec 2020 | 44 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | 200 | 24 | PRD4323105 |
IO102-IO103 | Test | LYOPHILIZED POWDER FOR PREPARATION FOR INJECTION (8) | SUBCUTANEOUS INJECTION | 170 | 24 | PRD9294901 |