Metastatic Non Small Cell Lung CancerPhase 2COMBI-TEDNCT04884282
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)
A Phase 2 study testing Tedopi, Nivolumab and Docetaxel in people with Metastatic Non Small Cell Lung Cancer, run by Fondazione Ricerca Traslazionale at 23 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Non Small Cell Lung Cancer
- What is being tested?
- Tedopi, Nivolumab and Docetaxel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 23 sitesin 3 countries
- Study dates
- 12 Oct 2021to 30 Sep 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 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;
- 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;
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- 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);
- Normal level of creatinine;
- 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.
- 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.
Who cannot join
- 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;
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- 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 locations and contacts
23 sites in 3 countries.
23 sites in 3 countries
Italy13 sites
Ospedale San Paolo
Civitavecchia
Azienda Ospedaliero-Universitaria Careggi
Florence
Ospedale Mater Salutis Legnago
Legnago, Verona, 37045
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, Forlì, 47014
AOOR Papardo-Piemonte
Messina
Ospedale Sacro Cuore Don Calabria
Negrar, Verona
AOU "Maggiore della Carità"
Novara
Istituto Oncologico Veneto
Padova, 35128
Azienda Ospedaliera di Perugia
Perugia
IRCCS - Arcispedale Santa Maria Nuova
Reggio Emilia
Istituto Nazionale Tumori "Regina Elena"
Roma, 00144
AO Busto Arstizio PO Saronno
Saronno, Varese
ASST Sette Laghi
Varese
Spain6 sites
Complejo Hospitalario Universitario A Coruña (CHUAC)
A Coruña, 15006
Clinica Mi Tres Torres - UOMI Cancer Center
Barcelona, 08017
Vall d'Hebron Universitary Hospital
Barcelona, 08035
Hospital Universitario La Paz
Madrid, 28046
Hospital Universitario Regional de Málaga - Hospital Civil
Málaga, 29011
Hospital de Mataró
Mataró, 08304
France4 sites
Institut Sainte Catherine
Avignon, 84918
Centre Hospitalier de Cholet
Cholet, 49300
GHR Mulhouse Sud Alsace - Hôpital Emile Muller
Mulhouse, 68100
Nouvel Hôpital Civil - Hopitaux Universitaires de Strasbourg
Strasbourg, 67091
About this study
Official title: A Multicenter, Phase II, Open Label, Randomized Trial Evaluating the 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)
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
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TedopiDrug
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)
NivolumabDrug
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.
DocetaxelDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A - tedopi + docetaxel | Experimental | 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. Receives: Drug: Tedopi; Drug: Docetaxel |
| Arm B - tedopi + nivolumab | Experimental | 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 Receives: Drug: Tedopi; Drug: Nivolumab |
| Arm C - docetaxel | Other | Docetaxel every 3 weeks until disease progression, unacceptable toxicity, patient refusal, or for a maximum of 6 cycles (whichever comes first). Receives: Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
1-year Survival Rate
1-year Survival Rate
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2021
- Study start12 Oct 2021
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Non Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 105 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione Ricerca Traslazionale
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04884282
- Sponsor's protocol ID
- COMBI-TED
- Acronym
- COMBI-TED
- Status last verified
- Feb 2026
- First submitted
- 11 May 2021
- Last updated
- 6 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 36946237
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Phase II, Open Label, Randomized Trial Evaluating the 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)
- ClinicalTrials.gov ID
- NCT04884282
- Acronym / sponsor ID
- COMBI-TED / COMBI-TED
- Conditions
- Metastatic Non Small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 105 participants (estimated)
- Lead sponsor
- Fondazione Ricerca TraslazionaleUniversity, hospital or other
- Study start
- 12 Oct 2021 (actual)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Sep 2028 (estimated)
- First posted
- 12 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Arm A - tedopi + docetaxel | Experimental | Drug: Tedopi, Drug: DocetaxelTedopi 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. |
| Arm B - tedopi + nivolumab | Experimental | Drug: Tedopi, Drug: NivolumabTedopi 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 |
| Arm C - docetaxel | Other | Drug: DocetaxelDocetaxel every 3 weeks until disease progression, unacceptable toxicity, patient refusal, or for a maximum of 6 cycles (whichever comes first). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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 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;
- 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);
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TedopiTEDOPI 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) | Drug | Arm A - tedopi + docetaxel, Arm B - tedopi + nivolumab |
| NivolumabNivolumab 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. | Drug | Arm B - tedopi + nivolumab |
| DocetaxelDocetaxel 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. | Drug | Arm A - tedopi + docetaxel, Arm C - docetaxel |
Primary outcome
1-year Survival Rate
Time frame: 1 year
1-year Survival Rate
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2026.
- Derived from this study: PubMed 36946237Landi 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
23 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tedopi, Nivolumab and Docetaxel in people with Metastatic Non Small Cell Lung Cancer, run by Fondazione Ricerca Traslazionale at 23 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Italy, Spain, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
1-year Survival Rate (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04884282, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2026.