Phase II Randomized Trial of Tedopi with Docetaxel or Nivolumab in Metastatic NSCLC Post-Chemoimmunotherapy
- Trial ID
- 2024-518224-74-01
- Protocol
- COMBI-TED
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this multicenter, Phase II, open-label, randomized trial is to assess the **1-year survival rate** in patients with metastatic non-small-cell lung cancer (NSCLC) who are treated with Tedopi plus docetaxel (arm A), Tedopi plus nivolumab (arm B), or docetaxel as a single agent (arm C) after progression on first-line chemoimmunotherapy. This objective is clinically relevant as it aims to determine the efficacy of these treatment combinations in extending survival in a patient population with limited therapeutic options.
Secondary objectives include:
- To assess **Overall Survival (OS)**
- To assess **Progression-free survival (PFS)**
- To assess **Objective Response Rate (ORR)**
- To assess treatment safety
- To assess the correlation of ORR, PFS, and OS with biomarkers in tumor tissue or blood
Participants
The clinical trial involves participants diagnosed with **metastatic non-small-cell lung cancer** (NSCLC) who are being assessed for a 1-year survival rate following treatment with Tedopi plus docetaxel, Tedopi plus nivolumab, or docetaxel as a single agent. The study population includes both male and female subjects aged 18 years and older, with a performance status of 0-1 on the ECOG scale. Participants are required to have a histological or cytological confirmed diagnosis of HLA-A2+ NSCLC without evidence of EGFR mutations or ALK or ROS1 rearrangement. They must have experienced disease progression after at least four cycles of chemoimmunotherapy or two cycles of chemo-immunotherapy followed by two cycles of immunotherapy. The trial excludes individuals with primary resistance to immunotherapy. Participants must have adequate bone marrow and liver function, and normal creatinine levels. The sponsor has not provided the total number of participants involved in the trial. The selection criteria ensure that participants are not part of a vulnerable population and are compliant with trial procedures. Lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is a multicenter, Phase II, open-label, randomized study designed to evaluate the efficacy of **Tedopi** in combination with either **docetaxel** or **nivolumab** as a second-line therapy for patients with metastatic non-small-cell lung cancer (NSCLC) who have progressed after first-line chemo-immunotherapy. The trial aims to assess the 1-year survival rate as the primary endpoint, with secondary endpoints including overall survival, progression-free survival, objective response rate, safety, and the correlation of these outcomes with tumor biomarkers. The study is expected to run from May 2022 to May 2026, with an estimated participant involvement duration of up to 36 months.
The trial design involves randomization of participants into three arms: Arm A receiving Tedopi plus docetaxel, Arm B receiving Tedopi plus nivolumab, and Arm C receiving docetaxel as a single agent. The study is not blinded, allowing both participants and investigators to know the treatment assignments. Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on inclusion criteria such as age, performance status, and adequate organ function. The screening visit will also ensure the absence of specific genetic mutations and the presence of disease progression after prior treatment.
Following the screening, participants will attend regular follow-up visits to monitor treatment response and safety. These visits will include assessments such as imaging studies, laboratory tests, and physical examinations. The end-of-study visit will occur at the conclusion of the treatment period or upon early termination, which may be due to disease progression, unacceptable toxicity, or withdrawal of consent. Participants are expected to comply with trial procedures throughout the study duration, and any deviation from protocol requirements may result in early termination from the trial.
Treatment
The clinical trial involves the administration of **Nivolumab**, an experimental medication, which is a monoclonal antibody used in the treatment of metastatic non-small-cell lung cancer (NSCLC). Nivolumab is administered in the form of a solution for intravenous use. The maximum daily dose is 360 mg, and the treatment period can extend up to 36 months. The administration frequency is determined by the study protocol, and compliance is monitored through regular assessments. Nivolumab is classified under the ATC code L01XC17 and is known by synonyms such as BMS936558 and ABP 206. The active substance is derived from a protein of other origin.
Another experimental treatment in the trial is **Tedopi**, a T-specific immunotherapy, also known as a cancer therapeutic vaccine. Tedopi is administered as an emulsion for injection via subcutaneous injection. The maximum daily dose is 5 mg/ml, with a treatment period of up to 24 months. Tedopi comprises multiple active substances, including MPS-112, MPS-106, MPS-213, MPS-102, MPS-216, MPS-103, MPS-215, MPS-214, D-ALA-LYS-CHA-VAL-ALA-ALA-TRP-THR-LEU-LYS-ALA-ALA-D-ALA, and MPS-200. These substances are proteins of other origin, and the product is developed by OSE Immunotherapeutics. The administration schedule and participant compliance are closely monitored throughout the study.
In addition to the experimental treatments, the trial includes a comparator treatment with **Docetaxel**, a standard-of-care chemotherapy agent for NSCLC. Docetaxel is administered according to the standard dosing regimen for the condition, and its use serves as a control to evaluate the efficacy of the experimental treatments. The trial aims to assess the 1-year survival rate in patients receiving Tedopi plus Docetaxel, Tedopi plus Nivolumab, or Docetaxel alone as second-line therapy in subjects with advanced NSCLC progressing on first-line chemoimmunotherapy.
Efficacy
The efficacy of the clinical trial will be assessed through a series of predefined endpoints. The primary endpoint is the 1-year survival rate in patients with metastatic non-small-cell lung cancer (NSCLC) treated with Tedopi plus docetaxel, Tedopi plus **nivolumab**, or docetaxel alone. Secondary endpoints include overall survival (OS) at 1 and 2 years, progression-free survival (PFS) at 1 and 2 years, objective response rate (ORR), safety, and the correlation of ORR, PFS, and OS with tumor biomarkers.
Data collection will occur at specified intervals throughout the trial, with survival rates and progression metrics being key indicators of efficacy. The analysis will involve comparing the survival and response rates across the different treatment arms to determine the relative efficacy of the combinations involving Tedopi and **nivolumab**. The trial is designed to provide comprehensive insights into the therapeutic potential of these combinations in a second-line treatment setting for NSCLC patients who have progressed after first-line chemo-immunotherapy.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male and female patients willing and able to give written informed consent
- Histological or cytological confirmed diagnosis of HLA-A2+ NSCLC with no evidence of EGFR mutations or ALK or ROS1 rearrangement
- Evidence of disease progression at the end of at least 4 cycles of chemoimmunotherapy or 2 cycles of chemo-immunotherapy followed by 2 cycles of immunotherapy (CheckMate9LA regimen) and eligible for treatment with docetaxel. Any chemotherapy is allowed, including chemotherapy containing platinum salts. This criterion implies that patients with immunotherapy primary resistance are excluded;
- Patients must have experienced progressive disease (PD), either during or within 3 months of discontinuing treatment with anti-PD-(L)1-based therapy, occurring after previous clear benefit (any complete –CR- or partial response -PR), or after previous stable disease (SD);
- Performance status 0-1 (ECOG)
- Patient compliance to trial procedures
- Age = 18 years
- Adequate BM function (ANC = 1.5x109/L, Platelets = 100x109/L, HgB > 9g/dl)
- Adequate liver function (bilirubin < G2, transaminases no more than 3xULN/<5xULN in present of liver metastases), no sever liver failure
- Normal level of creatinine
- Female patient: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of highly effective contraception methods (see paragraph 12.1.2) during treatment and for the time detailed in paragraph 12.1. or Male patient: should practice complete abstinence or if sexually active with WOCBP must use highly effective contraceptive methods and they should not donate semen as detailed in paragraph 12.1.
- Prior palliative radiotherapy to non-CNS lesions must have been completed at least 2 weeks prior to treatment. Subjects with symptomatic tumor lesions that may require palliative radiotherapy within 4 weeks of first treatment are strongly encouraged to receive palliative radiotherapy prior to treatment. Patients are eligible if CNS metastases are adequately treated and patients are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to randomization
- Patients must be either off corticosteroids, or on a stable or decreasing dose of =10 mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization
Exclusion Criteria
- Patient positive for actionable EGFR mutations or ALK or ROS1 rearrangement;
- No previous chemoimmunotherapy for metastatic disease or evidence of disease progression during the first 4 cycles of chemoimmunotherapy (primary resistance). Patients with adjuvant resistance (documented loco-regionally and/or systemic relapse of their disease occurring <6 months after the last dose of anti-PD-(L)1-based systemic adjuvant therapy) are excluded
- Patients with intervening systemic therapy following prior anti-PD-(L)1-based therapy
- Symptomatic brain metastases. Asymptomatic brain metastases are allowed if not requiring corticosteroids use at a dose >10mg daily prednisone (or equivalent)
- Diagnosis of any other malignancy during the last 3 years, except for in situ carcinoma of cervix uteri and cutaneous squamous cell carcinoma or other local tumors considered cured
- Pregnancy or lactating
- Patients with an active, known or suspected autoimmune disease. Patients with type I diabetes mellitus; hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
- Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
- Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection
- Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Recruiting | 17 May 2022 | 25 |
 Italy | Recruiting | 17 May 2022 | 55 |
 Spain | Recruiting | 17 May 2022 | 25 |
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 |
|---|---|---|---|---|---|---|
NIVOLUMAB | Test | PHF00230MIG | INTRAVENOUS USE | 360 | 36 | SCP8265340 |
TEDOPI | Test | EMULSION FOR INJECTION | SUBCUTANEOUS INJECTION | 5 | 24 | PRD11292393 |