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)

Last updated: September 15, 2023
Sponsor: Fondazione Ricerca Traslazionale
Overall Status: Active - Recruiting

Phase

2

Condition

N/A

Treatment

Tedopi

Docetaxel

Nivolumab

Clinical Study ID

NCT04884282
COMBI-TED
  • Ages > 18
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

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 ofEGFR mutations or ALK or ROS1 rearrangement;
  3. Evidence of disease progression at the end of at least 4 cycles of chemo-immunotherapyor 2 cycles of chemo-immunotherapy followed by 2 cycles of immunotherapy (CheckMate9LAregimen) and eligible for treatment with docetaxel. This criterion implies thatpatients with immunotherapy primary resistance are excluded;
  4. Patients must have experienced progressive disease (PD), either during or within 3months of discontinuing treatment with anti-PD-(L)1-based therapy, occurring afterprevious clear benefit (any complete -CR- or partial response -PR), or after previousstable 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 inpresent of liver metastases);
  10. Normal level of creatinine;
  11. Female patient: childbearing potential either terminated by surgery, radiation, ormenopause, 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 WOCBPmust use any contraceptive method with failure rate less than 1%/year and they shouldnot donate semen as follows: in arm A and C until 6 months since the last dose ofdocetaxel; 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 2weeks prior to treatment. Subjects with symptomatic tumor lesions that may requirepalliative radiotherapy within 4 weeks of first treatment are strongly encouraged toreceive palliative radiotherapy prior to treatment. Patients are eligible if CNSmetastases are adequately treated and patients are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2weeks prior to randomization;
  13. Patients must be either off corticosteroids, or on a stable or decreasing dose of ≤10mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization.

Exclusion

Exclusion Criteria:

  1. Patient positive for actionable EGFR mutations or ALK or ROS1 rearrangement;
  2. No previous chemoimmunotherapy for metastatic disease or evidence of diseaseprogression during the first 4 cycles of chemoimmunotherapy (primary resistance).Patients with adjuvant resistance (documented loco-regionally and/or systemic relapseof their disease occurring <6 months after the last dose of anti-PD-(L)1-basedsystemic 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 notrequiring corticosteroids use at a dose >10mg daily prednisone (or equivalent);
  5. Diagnosis of any other malignancy during the last 3 years, except for in situcarcinoma of cervix uteri and cutaneous squamous cell carcinoma or other local tumorsconsidered cured;
  6. Pregnancy or lactating;
  7. Patients with an active, known or suspected autoimmune disease. Patients with type Idiabetes mellitus; hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) requiring systemic treatment, or conditionsnot 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 14days of randomization. Inhaled or topical steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmunedisease;
  9. Patients should be excluded if they are positive test for hepatitis B virus surfaceantigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute orchronic infection;
  10. Patients should be excluded if they have known history of testing positive for humanimmunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).

Study Design

Total Participants: 105
Treatment Group(s): 3
Primary Treatment: Tedopi
Phase: 2
Study Start date:
October 12, 2021
Estimated Completion Date:
May 17, 2025

Connect with a study center

  • Institut Sainte Catherine

    Avignon, 84918
    France

    Active - Recruiting

  • Centre Hospitalier de Cholet

    Cholet, 49300
    France

    Active - Recruiting

  • GHR Mulhouse Sud Alsace - Hôpital Emile Muller

    Mulhouse, 68100
    France

    Active - Recruiting

  • Nouvel Hôpital Civil - Hopitaux Universitaires de Strasbourg

    Strasbourg, 67091
    France

    Active - Recruiting

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

    Meldola, Forlì 47014
    Italy

    Active - Recruiting

  • AO Busto Arstizio PO Saronno

    Saronno, Varese
    Italy

    Site Not Available

  • Ospedale Mater Salutis Legnago

    Legnago, Verona 37045
    Italy

    Active - Recruiting

  • Ospedale Sacro Cuore Don Calabria

    Negrar, Verona
    Italy

    Active - Recruiting

  • Ospedale San Paolo

    Civitavecchia,
    Italy

    Active - Recruiting

  • Azienda Ospedaliero-Universitaria Careggi

    Firenze,
    Italy

    Active - Recruiting

  • AOOR Papardo-Piemonte

    Messina,
    Italy

    Active - Recruiting

  • AOU "Maggiore della Carità"

    Novara,
    Italy

    Active - Recruiting

  • Istituto Oncologico Veneto

    Padova, 35128
    Italy

    Active - Recruiting

  • Azienda Ospedaliera di Perugia

    Perugia,
    Italy

    Active - Recruiting

  • IRCCS - Arcispedale Santa Maria Nuova

    Reggio Emilia,
    Italy

    Site Not Available

  • Istituto Nazionale Tumori "Regina Elena"

    Roma, 00144
    Italy

    Active - Recruiting

  • ASST Sette Laghi

    Varese,
    Italy

    Site Not Available

  • Complejo Hospitalario Universitario A Coruña (CHUAC)

    A Coruña, 15006
    Spain

    Active - Recruiting

  • Clinica Mi Tres Torres - UOMI Cancer Center

    Barcelona, 08017
    Spain

    Active - Recruiting

  • Vall d'Hebron Universitary Hospital

    Barcelona, 08035
    Spain

    Active - Recruiting

  • Hospital Universitario La Paz

    Madrid, 28046
    Spain

    Site Not Available

  • Hospital de Mataró

    Mataró, 08304
    Spain

    Active - Recruiting

  • Hospital Universitario Regional de Málaga - Hospital Civil

    Málaga, 29011
    Spain

    Active - Recruiting

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