Efficacy of Tedopi Plus Docetaxel or Tedopi Plus Nivolumab as Second-line Therapy in Metastatic Non-small-cell Lung Cancer Progressing After First-line Chemo-immunotherapy (Combi-TED)

NCT ID: NCT04884282

Last Updated: 2023-09-18

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-12
• Study Completion Date: 2025-05-17

Brief Summary

This is a phase II, non-comparative, randomized study assessing combination of Tedopi with docetaxel or with nivolumab in NSCLC patients failing after first- line chemoimmunotherapy. In this non-comparative study, the standard arm (arm C) will serve as a calibration arm. All NSCLC patients candidate for second- line therapy are considered eligible for the study if they are HLA-A2+ and if they progressed after at least 4 cycles of previous first-line chemo-immunotherapy. After evaluation of all inclusion and exclusion criteria and after informed consent signature, all eligible patients will be treated with Tedopi plus docetaxel (arm A) or Tedopi plus nivolumab (arm B) or docetaxel as single agent (arm C- standard arm). Docetaxel therapy will be given until disease progression, unacceptable toxicity or patient refusal, and up to maximum 6 cycles. Tedopi or nivolumab will be given until disease progression, unacceptable toxicity or patient refusal.

Conditions

Metastatic Non Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A - tedopi + docetaxel

Tedopi every 3 weeks plus docetaxel every 3 weeks only for 6 cycles, then maintenance with Tedopi alone every 6 weeks until the end of year 1, then every 12 weeks until disease progression, unacceptable toxicity or patient refusal.

Group Type: EXPERIMENTAL

Tedopi

Intervention Type: DRUG

TEDOPI is a T-specific immunotherapy was designed to induce cytotoxic T-lymphocytes against five five tumor associated antigens (ie CEA, p53, HER-2/neu, MAGE2 and MAGE3)

Docetaxel

Intervention Type: DRUG

Docetaxel is a cytotoxic microtubule inhibiting antineoplastic agent in the taxane class. Docetaxel monotherapy is indicated for locally advanced or metastatic NSCLC after failure of prior platinum- based chemotherapy.

Arm B - tedopi + nivolumab

Tedopi every 3 weeks plus nivolumab 360 mg every 3 weeks for 6 cycles, then maintenance nivolumab 360 mg every 3 weeks plus Tedopi every 6 weeks until the end of year 1, then every 12 weeks until disease progression, unacceptable toxicity or patient refusal

Group Type: EXPERIMENTAL

Tedopi

Intervention Type: DRUG

TEDOPI is a T-specific immunotherapy was designed to induce cytotoxic T-lymphocytes against five five tumor associated antigens (ie CEA, p53, HER-2/neu, MAGE2 and MAGE3)

Nivolumab

Intervention Type: DRUG

Nivolumab is a soluble protein consisting of 4 polypeptide chains, which include 2 identical heavy chains and 2 identical light chains. Nivolumab is produced from cell culture using a CHO cell line.

Arm C - docetaxel

Docetaxel every 3 weeks until disease progression, unacceptable toxicity, patient refusal, or for a maximum of 6 cycles (whichever comes first).

Group Type: OTHER

Docetaxel

Intervention Type: DRUG

Docetaxel is a cytotoxic microtubule inhibiting antineoplastic agent in the taxane class. Docetaxel monotherapy is indicated for locally advanced or metastatic NSCLC after failure of prior platinum- based chemotherapy.

Interventions

Tedopi

TEDOPI is a T-specific immunotherapy was designed to induce cytotoxic T-lymphocytes against five five tumor associated antigens (ie CEA, p53, HER-2/neu, MAGE2 and MAGE3)

Intervention Type: DRUG

Nivolumab

Nivolumab is a soluble protein consisting of 4 polypeptide chains, which include 2 identical heavy chains and 2 identical light chains. Nivolumab is produced from cell culture using a CHO cell line.

Intervention Type: DRUG

Docetaxel

Docetaxel is a cytotoxic microtubule inhibiting antineoplastic agent in the taxane class. Docetaxel monotherapy is indicated for locally advanced or metastatic NSCLC after failure of prior platinum- based chemotherapy.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male and female patients willing and able to give written informed consent;

2. Histological or cytological confirmed diagnosis of HLA-A2+ NSCLC with no evidence of EGFR mutations or ALK or ROS1 rearrangement;

3. Evidence of disease progression at the end of at least 4 cycles of chemo-immunotherapy or 2 cycles of chemo-immunotherapy followed by 2 cycles of immunotherapy (CheckMate9LA regimen) and eligible for treatment with docetaxel. This criterion implies that patients with immunotherapy primary resistance are excluded;

4. 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);

5. Performance status 0-1 (ECOG);

6. Patient compliance to trial procedures;

7. Age ≥ 18 years;

8. Adequate BM function (ANC ≥ 1.5x109/L, Platelets ≥ 100x109/L, HgB > 9g/dl);

9. Adequate liver function (bilirubin < G2, transaminases no more than 3xULN/<5xULN in present of liver metastases);

10. Normal level of creatinine;

11. Female patient: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of approved contraceptive method [complete abstinence, intrauterine contraceptive device (IUD), birth control pills, or barrier device] until 5 months after end of treatment.

or Male patient: should practice complete abstinence or if sexually active with WOCBP must use any contraceptive method with failure rate less than 1%/year and they should not donate semen as follows: in arm A and C until 6 months since the last dose of docetaxel; in arm B until 3 months since last dose of tedopi.

12. 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;

13. 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

1. Patient positive for actionable EGFR mutations or ALK or ROS1 rearrangement;

2. 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;

3. Patients with intervening systemic therapy following prior anti-PD-(L)1-based therapy;

4. Symptomatic brain metastases. Asymptomatic brain metastases are allowed if not requiring corticosteroids use at a dose >10mg daily prednisone (or equivalent);

5. 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;

6. Pregnancy or lactating;

7. 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;

8. 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;

9. 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;

10. Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione Ricerca Traslazionale

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institut Sainte Catherine

Avignon, , France

Site Status: RECRUITING

Centre Hospitalier de Cholet

Cholet, , France

Site Status: RECRUITING

GHR Mulhouse Sud Alsace - Hôpital Emile Muller

Mulhouse, , France

Site Status: RECRUITING

Nouvel Hôpital Civil - Hopitaux Universitaires de Strasbourg

Strasbourg, , France

Site Status: RECRUITING

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Forlì, Italy

Site Status: RECRUITING

AO Busto Arstizio PO Saronno

Saronno, Varese, Italy

Site Status: NOT_YET_RECRUITING

Ospedale Mater Salutis Legnago

Legnago, Verona, Italy

Site Status: RECRUITING

Ospedale Sacro Cuore Don Calabria

Negrar, Verona, Italy

Site Status: RECRUITING

Ospedale San Paolo

Civitavecchia, , Italy

Site Status: RECRUITING

Azienda Ospedaliero-Universitaria Careggi

Florence, , Italy

Site Status: RECRUITING

AOOR Papardo-Piemonte

Messina, , Italy

Site Status: RECRUITING

AOU "Maggiore della Carità"

Novara, , Italy

Site Status: RECRUITING

Istituto Oncologico Veneto

Padua, , Italy

Site Status: RECRUITING

Azienda Ospedaliera di Perugia

Perugia, , Italy

Site Status: RECRUITING

IRCCS - Arcispedale Santa Maria Nuova

Reggio Emilia, , Italy

Site Status: NOT_YET_RECRUITING

Istituto Nazionale Tumori "Regina Elena"

Roma, , Italy

Site Status: RECRUITING

ASST Sette Laghi

Varese, , Italy

Site Status: NOT_YET_RECRUITING

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, , Spain

Site Status: RECRUITING

Clinica Mi Tres Torres - UOMI Cancer Center

Barcelona, , Spain

Site Status: RECRUITING

Vall d'Hebron Universitary Hospital

Barcelona, , Spain

Site Status: RECRUITING

Hospital Universitario La Paz

Madrid, , Spain

Site Status: NOT_YET_RECRUITING

Hospital de Mataró

Mataró, , Spain

Site Status: RECRUITING

Hospital Universitario Regional de Málaga - Hospital Civil

Málaga, , Spain

Site Status: RECRUITING

Countries

France; Italy; Spain

Central Contacts

Federico Cappuzzo, MD

Role: CONTACT

f.cappuzzo@gmail.com

+39 06.5266.5698

Facility Contacts

François-Roger Vanel

Role: primary

Sylvère Guillemois

Role: primary

Didier Debieuvre

Role: primary

Céline Mascaux

Role: primary

Angelo Delmonte

Role: primary

Claudio Verusio

Role: primary

Daniela Mangiola

Role: primary

Stefania Gori

Role: primary

Mario Rosario D'Andrea

Role: primary

Francesca Mazzoni

Role: primary

Antonino Scimone

Role: primary

Gloria Borra

Role: primary

Giulia Pasello

Role: primary

Giulio Metro

Role: primary

Maria Pagano

Role: primary

Federico Cappuzzo

Role: primary

Alessandro Tuzzi

Role: primary

Maria Rosario Garcia Campelo

Role: primary

Santiago Viteri

Role: primary

Enriqueta Felip

Role: primary

Javier De Castro

Role: primary

Laura Puntì Brun

Role: primary

Manuel Cobo Dols

Role: primary

References

Landi L, Delmonte A, Bonetti A, Pasello G, Metro G, Mazzoni F, Borra G, Giannarelli D, Andrikou K, Mangiola D, Gori S, D'Andrea MR, Minuti G, Resuli B, Laudisi A, Vidiri A, Conti L, Cappuzzo F. Combi-TED: a new trial testing Tedopi(R) with docetaxel or nivolumab in metastatic non-small-cell lung cancer progressing after first line. Future Oncol. 2022 Dec;18(40):4457-4464. doi: 10.2217/fon-2022-0913. Epub 2023 Mar 22.

Reference Type: DERIVED

PMID: 36946237 (View on PubMed)

Other Identifiers

COMBI-TED

Identifier Type: -

Identifier Source: org_study_id