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-smallcell lung cancer progressing after first-line chemo-immunotherapy (Combi-TED)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondazione Ricerca Traslazionale

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 Feb 2025 → ongoing

Decision date (initial)

2025-02-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518224-74-01

EudraCT number

2020-005170-10

ClinicalTrials.gov

NCT04884282

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

To assess 1-year survival rate in patients treated with Tedopi plus docetaxel (arm A)
or Tedopi plus nivolumab (arm B) or docetaxel as single agent (arm C) in subjects
with advanced NSCLC progressing on first-line chemoimmunotherapy.

Secondary objectives 5

1. To assess Overall Survival (OS)
2. To assess Progression-free survival (PFS)
3. To assess Objective Response Rate (ORR)
4. To assess treatment safety
5. To assess correlation of ORR, PFS and OS with biomarkers in tumor tissue or blood.

Conditions and MedDRA coding

metastatic non-small-cell lung cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

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 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;
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), no sever liver failure
10. Normal level of creatinine
11. 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.
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 10

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)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1-year Survival Rate

Secondary endpoints 5

1. Overall Survival (OS) (1 and 2-year OS)
2. Progression-free survival (PFS) (1 and 2-year PFS)
3. Objective Response rate (ORR)
4. Safety
5. Correlation of ORR, PFS and OS with tumor biomarkers

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondazione Ricerca Traslazionale

Sponsor organisation

Fondazione Ricerca Traslazionale

Address

Via Dei Santi Quattro 61

City

Rome

Postcode

00184

Country

Italy

Scientific contact point

Organisation

Fondazione Ricerca Traslazionale

Contact name

Federico Cappuzzo

Public contact point

Organisation

Fondazione Ricerca Traslazionale

Contact name

Fabrizio Cappuzzo

Locations

3 EU/EEA countries · 23 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 24 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications