A Phase 1/2 interventional study of Tocilizumab and Pembrolizumab in Metastatic Non-Small Cell Lung Cancer, Cancer-Associated Weight Loss and Elevated Inflammatory Markers, sponsored by VA Office of Research and Development. Not yet recruiting at 4 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-22.
Sponsored by VA Office of Research and Development · Phase 1/2, Interventional, and Treatment
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.
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 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 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.
6,641 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,665 are open to participants now.
This study's planned enrollment of 43 is below the median of 62 across 5,327 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.
Browse Carcinoma, Non-Small-Cell Lung studies →VA Office of Research and Development is the lead sponsor of 1,767 studies on the registry; 394 are open to participants now.
Of its 209 completed or terminated interventional studies of FDA-regulated products, 183 (88%) have results posted.
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Exclusion Criteria:
Tocilizumab + pembrolizumab + platinum doublet chemotherapy
Drug: Tocilizumab · Drug: Pembrolizumab · Drug: Platinum-Doublet Chemotherapy
Tocilizumab 8 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.
Also known as: Actemra, Actemra ACTPen, Tofidence, Tyenne
Pembrolizumab is administered per standard-of-care dosing every 21 days in combination with platinum-based doublet chemotherapy and tocilizumab.
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.
Also known as: Carboplatin plus pemetrexed; carboplatin plus taxane
Safety
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.
Time frame: From Day 1 of treatment through completion of Cycle 4 (approximately 12 weeks)
Progression-Free Survival Rate
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.
Time frame: 6 months after after initiation of study treatment
Feasibility of Treatment Completion
Proportion of patients completing four cycles of treatment. Feasibility is defined as ≥80% of patients completing all four cycles.
Time frame: From Day 1 of treatment through completion of Cycle 4 (approximately 12 weeks)
Weight Change
Measured from baseline to end of treatment (EOT) using objective weight data.
Time frame: Baseline to EOT (approximately 3 months)
Muscle Mass
Assessed via Computed Tomography (CT) -based analysis at baseline and end of treatment.
Time frame: at baseline and EOT (30 +/- 7 days post last dose)
Overall Response Rate (ORR)
Defined as complete response (CR) + partial response (PR) per RECIST 1.1 at end of treatment.
Time frame: at EOT (approximately 3 months)
Median Overall Survivial Rate
Time from Day 1 of treatment to the point at which 50% of participants have died and 50% remain alive.
Time frame: From Day 1 of treatment until death or last follow-up (up to 12 months post-EOT)
Inflammatory Biomarkers
Changes in C-Reactive Protein (CRP) levels from baseline to end of treatment.
Time frame: From baseline to EOT (30 +/- 7 days post last dose)
Sarcopenia
Assessed via CT-based analysis at baseline and end of treatment.
Time frame: at baseline and EOT (30 +/- 7 days post last dose)
Correlation between Baseline IL-6 and Overall Response Rate (ORR)
Evaluation of the association between baseline Interleukin-6 (IL-6) concentration and Objective Response Rate (ORR).
Time frame: Baseline
Correlation between Baseline CRP and Overall Response Rate (ORR)
Assessment of the relationship between baseline C-reactive protein (CRP) levels and ORR.
Time frame: Baseline
Correlation between Baseline PTPRT Methylation and Overall Response Rate (ORR)
Assessment of the association between baseline PTPRT methylation status and ORR.
Time frame: Baseline
Correlation between Baseline KRAS Mutation Status and Overall Response Rate (ORR)
Evaluation of the correlation between KRAS tumor mutational status at baseline and ORR.
Time frame: Baseline
Correlation between Baseline STK11 Mutation Status and Overall Response Rate (ORR)
Evaluation of the correlation between baseline STK11 tumor mutational status and ORR.
Time frame: Baseline
Correlation between Baseline IL-6 and PFS
Evaluation of the association between baseline IL-6 concentration and Progression-Free Survival (PFS).
Time frame: Baseline
Correlation between Baseline CRP and PFS
Assessment of the relationship between baseline CRP concentration and PFS.
Time frame: Baseline
Correlation between Baseline PTPRT Methylation and PFS
Assessment of the association between baseline PTPRT methylation status and PFS.
Time frame: Baseline
Correlation between Baseline KRAS Mutation Status and PFS
Evaluation of the correlation between KRAS mutation status at baseline and PFS.
Time frame: Baseline
Correlation between Baseline STK11 Mutation Status and PFS
Evaluation of the association between baseline STK11 mutation status and PFS.
Time frame: Baseline
Correlation between Longitudinal IL-6 Changes and Overall Response Rate (ORR)
Analysis of whether changes in IL-6 levels measured at Baseline, C1D1, C2D1, C3D1, C4D1, and End of Treatment correlate with ORR.
Time frame: Baseline through End of Treatment (30 +/- 7 days post last dose)
Correlation between Longitudinal CRP Changes and Overall Response Rate (ORR)
Analysis of whether changes in CRP levels measured at Baseline, C1D1, C2D1, C3D1, C4D1, and End of Treatment correlate with ORR.
Time frame: Baseline through End of Treatment (30 +/- 7 days post last dose)
Correlation between Longitudinal Cyclin D1 mRNA Changes and Overall Response Rate (ORR)
Assessment of whether changes in Cyclin D1 mRNA expression measured at Baseline, C1D1, C2D1, C3D1, C4D1, and End of Treatment correlate with ORR.
Time frame: Baseline through End of Treatment (30 +/- 7 days post last dose)
Correlation between Longitudinal Bcl-xL mRNA Changes and Overall Response Rate (ORR)
Evaluation of whether changes in Bcl-xL mRNA expression measured at Baseline, C1D1, C2D1, C3D1, C4D1, and End of Treatment correlate with ORR.
Time frame: Baseline through End of Treatment (30 +/- 7 days post last dose)
Correlation between Longitudinal IL-6 Changes and PFS
Evaluation of whether IL-6 level changes measured at Baseline, C1D1, C2D1, C3D1, C4D1, and End of Treatment correlate with PFS.
Time frame: Baseline through End of Treatment (30 +/- 7 days post last dose)
Correlation between Longitudinal CRP Changes and PFS
Evaluation of whether CRP level changes measured at Baseline, C1D1, C2D1, C3D1, C4D1, and End of Treatment correlate with PFS.
Time frame: Baseline through End of Treatment (30 +/- 7 days post last dose)
Correlation between Longitudinal Cyclin D1 mRNA Changes and PFS
Assessment of whether changes in Cyclin D1 mRNA measured at Baseline, C1D1, C2D1, C3D1, C4D1, and End of Treatment correlate with PFS.
Time frame: Baseline through End of Treatment (30 +/- 7 days post last dose)
Correlation between Longitudinal Bcl-xL mRNA Changes and PFS
Assessment of whether changes in Bcl-xL mRNA measured at Baseline, C1D1, C2D1, C3D1, C4D1, and End of Treatment correlate with PFS.
Time frame: Baseline through End of Treatment (30 +/- 7 days post last dose)
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Studies of the drug tested here: Tocilizumab
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