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

November 6, 2026 updated by: 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
43

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Indiana
      • Indianapolis, Indiana, United States, 46202-2884
    • Michigan
      • Ann Arbor, Michigan, United States, 48105-2303
    • Ohio
      • Cleveland, Ohio, United States, 44106-1702
        • Louis Stokes VA Medical Center, Cleveland, OH
        • Contact:
          • Margaret Tiktin, DNP
          • Phone Number: (216) 231-3241
        • Principal Investigator:
          • Charles J Nock, MD
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15240
        • VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Single Arm

Tocilizumab + pembrolizumab + platinum doublet chemotherapy
Drug: 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.

Other Names:
  • Actemra, Actemra ACTPen, Tofidence, Tyenne
Drug: Pembrolizumab

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

Drug: 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.

Other Names:
  • Carboplatin plus pemetrexed; carboplatin plus taxane

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety of adding Tocilizumab to Standard of Care Immunotherapy
Time Frame: 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
Time Frame: 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
Time Frame: 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)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Weight Change
Time Frame: 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
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Correlation between Baseline IL-6 and Overall Response Rate (ORR)
Time Frame: 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)
Time Frame: 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)
Time Frame: Baseline

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

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

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

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

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

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

Evaluation of the association between baseline STK11 mutation status and PFS.
Baseline
Correlation between Longitudinal IL-6 Changes and Overall Response Rate (ORR)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
VA Office of Research and Development

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Charles J Nock, MD, Louis Stokes VA Medical Center, Cleveland, OH

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 7, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 31, 2029

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 18, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 15, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 22, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 12, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 6, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SPLP-001-26S

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings