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Tocilizumab Combined With First-Line Chemo-Immunotherapy in Metastatic Non-Small Cell Lung Cancer (TOCI)

2026. november 6. frissítette: VA Office of Research and Development

A Phase 1b Study of Tocilizumab Combined With Chemo-Immunotherapy in Metastatic Non-Small Cell Lung Cancer Patients With Cancer-Associated Weight Loss and Elevated Inflammatory Markers. The TOCI Study

This is a Phase 1b/2, multi-site, single-arm, open-label, non-randomized study looking at whether adding tocilizumab to standard treatment for metastatic Non-Small Cell Lung Cancer (NSCLC) is safe, possible, and effective. The study includes people with metastatic NSCLC, that is lung cancer that has spread, who have experienced significant loss of weight or muscle mass.

A tanulmány áttekintése

Állapot

Még nincs toborzás

Körülmények

Beavatkozás / kezelés

Részletes leírás

Lung cancer remains the leading cause of cancer-related mortality globally, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all diagnoses. For patients with metastatic NSCLC lacking actionable driver mutations (e.g., EGFR, ALK), the standard first-line therapeutic strategy involves immune checkpoint inhibitors (ICIs) targeting the programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) axis, administered either as monotherapy or in combination with platinum-doublet chemotherapy. While these regimens have significantly improved overall survival (OS), a substantial proportion of patients fail to derive durable clinical benefit, and long-term survival rates for metastatic disease remain suboptimal, often due to host-related factors that impair the anti-tumor immune response.

A critical determinant of poor therapeutic outcomes in advanced NSCLC is cancer-associated cachexia (CAC), a multifactorial paraneoplastic syndrome characterized by systemic inflammation, negative protein-energy balance, and the involuntary loss of skeletal muscle mass (sarcopenia). Primary observational studies demonstrate that nutritional derangements closely associated with cachexia - such as significant weight loss and malnutrition - are highly prevalent in lung cancer, particularly in advanced disease, with lung cancer-specific cohorts reporting rates ranging from approximately 35% - 70% depending on disease stage and assessment method. Unlike starvation, it is driven by aberrant systemic inflammation and not fully reversible via nutritional support.

Clinically, cachexia is defined by the international consensus (Fearon criteria) as weight loss >5% over 6 months, or weight loss >2% in individuals with a body mass index (BMI) < 20 kilograms per square meter (kg/m2) or sarcopenia. Sarcopenia is specifically defined by a low skeletal muscle index (SMI) at the L3 vertebral level, with widely validated cutoffs of < 52.4 cm2/m2 for men and < 8.5 cm2/m2 for women.

This is a Phase 1b/2, multi-site, single-arm, open-label, non-randomized study looking at whether adding tocilizumab to standard treatment for metastatic Non-Small Cell Lung Cancer (NSCLC) is safe, possible, and effective. The study includes people with metastatic NSCLC, that is lung cancer that has spread, who have experienced significant loss of weight or muscle mass.

Primary Objective Evaluate the safety/feasibility and efficacy of adding tocilizumab to standard first-line chemo-immunotherapy in biomarker-selected patients with stage IV NSCLC, defined by weight loss ≥5% within the prior 6 months, or ≥2% if BMI < 20 kilograms per square meter (kg/m2).

Co-primary endpoint 1: Safety/Feasibility Proportion of patients completing four cycles of chemo-IO + tocilizumab without grade ≥3 autoimmune or non-hematological treatment-related adverse events (TRAE). Feasibility will be defined as ≥80% completion; unacceptable toxicity as >30% incidence of grade ≥3 serious AEs.

Co-primary endpoint 2: Progression-Free Survival Rate at 6 months Proportion of patients alive and progression-free at 6 months after starting therapy per RECIST v1.1, estimated by Kaplan-Meier and presented with a 95% CI.

Secondary Objectives Assess the effect of tocilizumab on body composition, inflammatory biomarkers, and treatment response.

Secondary Endpoints: change in weight/muscle mass (CT-based sarcopenia/Fearon index); Overall Response Rate (ORR); median Overall Survival Rate; and CRP levels from baseline to end of treatment.

Correlative Objectives Evaluate associations between treatment response (PFS rate at 6 months, ORR) and baseline inflammatory biomarkers (CRP) as well as molecular biomarkers (KRAS, STK11) identified by next-generation sequencing (NGS) of tumor tissue.

Exploratory Objectives Identify associations between treatment response (PFS rate at 6 months, ORR) and longitudinal measurements of CRP, IL-6, Cyclin D1 and Bcl-xL mRNA, as well as baseline PTPRT methylation.

Participants will go through the screening and baseline process to assess eligibility. If eligible, participants will attend study treatment visits every 21 days for about 3 months, an End of Treatment (EOT) visit about 30 days after the last dose of treatment, and follow up for up to 12 months after the EOT visit. Tocilizumab will be administered in addition to standard treatment regimens for NSCLC, at a dose of 8 mg/kg intravenous (IV) once every three weeks (once every 21 days); on day one of each treatment cycle. Tocilizumab is administered as a single IV drip infusion over 1 hour; it cannot be administered as bolus or push. Tocilizumab will be given for 4 doses, at the beginning of treatment, or until disease progression or unacceptable toxicities.

The study will be open at 4 VA hospitals, and planned enrollment is about 43 participants in total with about 11 participants from each site. This research study is expected to take about 4 years. Individual participation in the study will take about 18 months.

Tanulmány típusa

Beavatkozó

Beiratkozás (Becsült)

43

Fázis

  • 2. fázis
  • 1. fázis

Kapcsolatok és helyek

Ez a rész a vizsgálatot végzők elérhetőségeit, valamint a vizsgálat lefolytatásának helyére vonatkozó információkat tartalmazza.

Tanulmányi kapcsolat

Tanulmányi helyek

  • Egyesült Államok
    • Indiana
      • Indianapolis, Indiana, Egyesült Államok, 46202-2884
        • Richard L. Roudebush VA Medical Center, Indianapolis, IN
        • Kapcsolatba lépni:
        • Kapcsolatba lépni:
    • Michigan
      • Ann Arbor, Michigan, Egyesült Államok, 48105-2303
        • VA Ann Arbor Healthcare System, Ann Arbor, MI
        • Kapcsolatba lépni:
        • Kapcsolatba lépni:
    • Ohio
      • Cleveland, Ohio, Egyesült Államok, 44106-1702
        • Louis Stokes VA Medical Center, Cleveland, OH
        • Kapcsolatba lépni:
          • Margaret Tiktin, DNP
          • Telefonszám: (216) 231-3241
        • Kutatásvezető:
          • Charles J Nock, MD
    • Pennsylvania
      • Pittsburgh, Pennsylvania, Egyesült Államok, 15240
        • VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
        • Kapcsolatba lépni:
        • Kapcsolatba lépni:

Részvételi kritériumok

A kutatók olyan embereket keresnek, akik megfelelnek egy bizonyos leírásnak, az úgynevezett jogosultsági kritériumoknak. Néhány példa ezekre a kritériumokra a személy általános egészségi állapota vagy a korábbi kezelések.

Jogosultsági kritériumok

Tanulmányozható életkorok

18 év és régebbi (Felnőtt, Idősebb felnőtt)

Egészséges önkénteseket fogad

Nem

Tanulmányozható nemek

Összes

Leírás

Inclusion Criteria:

  1. Age ≥ 18 years at the time of consent
  2. Histologically confirmed metastatic Non-Small Cell Lung Cancer (NSCLC)
  3. No Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase (ALK), ROS Proto-Oncogene 1 (ROS1), or Rearranged During Transfection Proto-Oncogene (RET) mutations
  4. ≥ 5% unintentional weight loss or >2% if Body Mass Index (BMI) < 20 kilograms/square meter (kg/m2) in prior 6 months
  5. Candidate for platinum-doublet and Programmed Death-Ligand 1 (PD-L1) inhibitor
  6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
  7. Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  8. Baseline Interleukin-6 (IL-6) and C-reactive protein (CRP) available

Exclusion Criteria:

  1. Prior systemic therapy for metastatic disease
  2. Autoimmune disease requiring immunosuppression
  3. Active infection or high Gastrointestinal (GI) perforation risk
  4. Symptomatic brain metastasis
  5. Active hepatitis B infection
  6. Active or untreated latent Tuberculosis (TB) infection

Tanulási terv

Ez a rész a vizsgálati terv részleteit tartalmazza, beleértve a vizsgálat megtervezését és a vizsgálat mérését.

Hogyan készül a tanulmány?

Tervezési részletek

  • Elsődleges cél: Kezelés
  • Kiosztás: N/A
  • Beavatkozó modell: Egyetlen csoportos hozzárendelés
  • Maszkolás: Nincs (Open Label)

Fegyverek és beavatkozások

Résztvevő csoport / kar
Beavatkozás / kezelés
Kísérleti: Single Arm

Tocilizumab + pembrolizumab + platinum doublet chemotherapy
Drog: Tocilizumab

Tocilizumab 8 milligrams per kilogram (mg/kg) intravenous infusion administered once every 21 days (Day 1 of each cycle) for up to 4 doses. The drug is diluted in 0.9% or 0.45% sodium chloride and infused over 60 minutes. Tocilizumab is given in combination with pembrolizumab and platinum-based doublet chemotherapy. Dose reductions to 4 mg/kg are permitted per protocol in the setting of toxicity.

Más nevek:
  • Actemra, Actemra ACTPen, Tofidence, Tyenne
Drog: Pembrolizumab

Pembrolizumab is administered per standard-of-care dosing every 21 days in combination with platinum-based doublet chemotherapy and tocilizumab.

Drog: Platinum-Doublet Chemotherapy

Standard-of-care platinum doublet chemotherapy administered every 21 days in combination with pembrolizumab and tocilizumab, using either carboplatin with pemetrexed (non-squamous NSCLC) or carboplatin with a taxane (squamous NSCLC), per institutional guidelines.

Más nevek:
  • Carboplatin plus pemetrexed; carboplatin plus taxane

Mit mér a tanulmány?

Elsődleges eredményintézkedések

Eredménymérő
Intézkedés leírása
Időkeret
Safety of adding Tocilizumab to Standard of Care Immunotherapy
Időkeret: From Day 1 of treatment through completion of Cycle 4 (approximately 12 weeks)

Safety: Incidence of grade ≥3 non-hematological treatment-related adverse events (TRAEs) or autoimmune toxicities. Unacceptable toxicity is defined as more than 30% incidence of grade ≥3 serious adverse events (AEs), assessed by clinical and laboratory evaluation per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
From Day 1 of treatment through completion of Cycle 4 (approximately 12 weeks)
Progression-Free Survival Rate
Időkeret: 6 months after after initiation of study treatment

Progression-Free Survival Rate at 6 months: Time from Day 1 of treatment to documented disease progression or death, assessed at 6 months per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and calculated using Kaplan Meier statistics.
6 months after after initiation of study treatment
Feasibility of Treatment Completion
Időkeret: From Day 1 of treatment through completion of Cycle 4 (approximately 12 weeks)

Proportion of patients completing four cycles of treatment. Feasibility is defined as ≥80% of patients completing all four cycles.
From Day 1 of treatment through completion of Cycle 4 (approximately 12 weeks)

Másodlagos eredményintézkedések

Eredménymérő
Intézkedés leírása
Időkeret
Weight Change
Időkeret: Baseline to EOT (approximately 3 months)

Measured from baseline to end of treatment (EOT) using objective weight data.
Baseline to EOT (approximately 3 months)
Muscle Mass
Időkeret: at baseline and EOT (30 +/- 7 days post last dose)

Assessed via Computed Tomography (CT) -based analysis at baseline and end of treatment.
at baseline and EOT (30 +/- 7 days post last dose)
Overall Response Rate (ORR)
Időkeret: at EOT (approximately 3 months)

Defined as complete response (CR) + partial response (PR) per RECIST 1.1 at end of treatment.
at EOT (approximately 3 months)
Median Overall Survivial Rate
Időkeret: From Day 1 of treatment until death or last follow-up (up to 12 months post-EOT)

Time from Day 1 of treatment to the point at which 50% of participants have died and 50% remain alive.
From Day 1 of treatment until death or last follow-up (up to 12 months post-EOT)
Inflammatory Biomarkers
Időkeret: From baseline to EOT (30 +/- 7 days post last dose)

Changes in C-Reactive Protein (CRP) levels from baseline to end of treatment.
From baseline to EOT (30 +/- 7 days post last dose)
Sarcopenia
Időkeret: at baseline and EOT (30 +/- 7 days post last dose)

Assessed via CT-based analysis at baseline and end of treatment.
at baseline and EOT (30 +/- 7 days post last dose)

Egyéb eredményintézkedések

Eredménymérő
Intézkedés leírása
Időkeret
Correlation between Baseline IL-6 and Overall Response Rate (ORR)
Időkeret: Baseline

Evaluation of the association between baseline Interleukin-6 (IL-6) concentration and Objective Response Rate (ORR).
Baseline
Correlation between Baseline CRP and Overall Response Rate (ORR)
Időkeret: Baseline

Assessment of the relationship between baseline C-reactive protein (CRP) levels and ORR.
Baseline
Correlation between Baseline PTPRT Methylation and Overall Response Rate (ORR)
Időkeret: Baseline

Assessment of the association between baseline PTPRT methylation status and ORR.
Baseline
Correlation between Baseline KRAS Mutation Status and Overall Response Rate (ORR)
Időkeret: Baseline

Evaluation of the correlation between KRAS tumor mutational status at baseline and ORR.
Baseline
Correlation between Baseline STK11 Mutation Status and Overall Response Rate (ORR)
Időkeret: Baseline

Evaluation of the correlation between baseline STK11 tumor mutational status and ORR.
Baseline
Correlation between Baseline IL-6 and PFS
Időkeret: Baseline

Evaluation of the association between baseline IL-6 concentration and Progression-Free Survival (PFS).
Baseline
Correlation between Baseline CRP and PFS
Időkeret: Baseline

Assessment of the relationship between baseline CRP concentration and PFS.
Baseline
Correlation between Baseline PTPRT Methylation and PFS
Időkeret: Baseline

Assessment of the association between baseline PTPRT methylation status and PFS.
Baseline
Correlation between Baseline KRAS Mutation Status and PFS
Időkeret: Baseline

Evaluation of the correlation between KRAS mutation status at baseline and PFS.
Baseline
Correlation between Baseline STK11 Mutation Status and PFS
Időkeret: Baseline

Evaluation of the association between baseline STK11 mutation status and PFS.
Baseline
Correlation between Longitudinal IL-6 Changes and Overall Response Rate (ORR)
Időkeret: Baseline through End of Treatment (30 +/- 7 days post last dose)

Analysis of whether changes in IL-6 levels measured at Baseline, C1D1, C2D1, C3D1, C4D1, and End of Treatment correlate with ORR.
Baseline through End of Treatment (30 +/- 7 days post last dose)
Correlation between Longitudinal CRP Changes and Overall Response Rate (ORR)
Időkeret: Baseline through End of Treatment (30 +/- 7 days post last dose)

Analysis of whether changes in CRP levels measured at Baseline, C1D1, C2D1, C3D1, C4D1, and End of Treatment correlate with ORR.
Baseline through End of Treatment (30 +/- 7 days post last dose)
Correlation between Longitudinal Cyclin D1 mRNA Changes and Overall Response Rate (ORR)
Időkeret: Baseline through End of Treatment (30 +/- 7 days post last dose)

Assessment of whether changes in Cyclin D1 mRNA expression measured at Baseline, C1D1, C2D1, C3D1, C4D1, and End of Treatment correlate with ORR.
Baseline through End of Treatment (30 +/- 7 days post last dose)
Correlation between Longitudinal Bcl-xL mRNA Changes and Overall Response Rate (ORR)
Időkeret: Baseline through End of Treatment (30 +/- 7 days post last dose)

Evaluation of whether changes in Bcl-xL mRNA expression measured at Baseline, C1D1, C2D1, C3D1, C4D1, and End of Treatment correlate with ORR.
Baseline through End of Treatment (30 +/- 7 days post last dose)
Correlation between Longitudinal IL-6 Changes and PFS
Időkeret: Baseline through End of Treatment (30 +/- 7 days post last dose)

Evaluation of whether IL-6 level changes measured at Baseline, C1D1, C2D1, C3D1, C4D1, and End of Treatment correlate with PFS.
Baseline through End of Treatment (30 +/- 7 days post last dose)
Correlation between Longitudinal CRP Changes and PFS
Időkeret: Baseline through End of Treatment (30 +/- 7 days post last dose)

Evaluation of whether CRP level changes measured at Baseline, C1D1, C2D1, C3D1, C4D1, and End of Treatment correlate with PFS.
Baseline through End of Treatment (30 +/- 7 days post last dose)
Correlation between Longitudinal Cyclin D1 mRNA Changes and PFS
Időkeret: Baseline through End of Treatment (30 +/- 7 days post last dose)

Assessment of whether changes in Cyclin D1 mRNA measured at Baseline, C1D1, C2D1, C3D1, C4D1, and End of Treatment correlate with PFS.
Baseline through End of Treatment (30 +/- 7 days post last dose)
Correlation between Longitudinal Bcl-xL mRNA Changes and PFS
Időkeret: Baseline through End of Treatment (30 +/- 7 days post last dose)

Assessment of whether changes in Bcl-xL mRNA measured at Baseline, C1D1, C2D1, C3D1, C4D1, and End of Treatment correlate with PFS.
Baseline through End of Treatment (30 +/- 7 days post last dose)

Együttműködők és nyomozók

Itt találhatja meg a tanulmányban érintett személyeket és szervezeteket.

Szponzor

VA Office of Research and Development

Nyomozók

  • Kutatásvezető: Charles J Nock, MD, Louis Stokes VA Medical Center, Cleveland, OH

Tanulmányi rekorddátumok

Ezek a dátumok nyomon követik a ClinicalTrials.gov webhelyre benyújtott vizsgálati rekordok és összefoglaló eredmények benyújtásának folyamatát. A vizsgálati feljegyzéseket és a jelentett eredményeket a Nemzeti Orvostudományi Könyvtár (NLM) felülvizsgálja, hogy megbizonyosodjon arról, hogy megfelelnek-e az adott minőség-ellenőrzési szabványoknak, mielőtt közzéteszik őket a nyilvános weboldalon.

Tanulmány főbb dátumok

Tanulmány kezdete (Becsült)

2026. december 7.

Elsődleges befejezés (Becsült)

2029. május 31.

A tanulmány befejezése (Becsült)

2029. november 30.

Tanulmányi regisztráció dátumai

Először benyújtva

2026. szeptember 18.

Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak

2026. október 15.

Első közzététel (Tényleges)

2026. október 22.

Tanulmányi rekordok frissítései

Utolsó frissítés közzétéve (Tényleges)

2026. november 12.

Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak

2026. november 6.

Utolsó ellenőrzés

2026. november 1.

Több információ

A tanulmányhoz kapcsolódó kifejezések

További vonatkozó MeSH feltételek

Egyéb vizsgálati azonosító számok

  • SPLP-001-26S

Terv az egyéni résztvevői adatokhoz (IPD)

Tervezi megosztani az egyéni résztvevői adatokat (IPD)?

NEM

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Nem

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Nem

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