Personalized Escalation of Consolidation Treatment Following Chemoradiotherapy and Immunotherapy in Stage III NSCLC in Stage III NSCLC

NCT04585490 | Recruiting Phase 3 DMC FDA Drug FDA Device

• 3 other identifiers: IRB-54807LUN0114NCI-2021-09500
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test whether or not number of circulating cancer cells detected in the blood can be decreased the by combining the standard treatment (durvalumab) with Tremelimumab and additional chemotherapy

Conditions

NSCLC, Stage III; Nsclc; Non Small Cell Lung Cancer

Keywords

durvalumab; tremelimumab

Outcome Measures

Primary Outcomes (1)

• Change in ctDNA Level Following Chemotherapy

  Participants in Cohort 1 MRD+ will be assessed for ctDNA levels at baseline and end of treatment, expected to be 4 cycles of 3 weeks per cycle (defined as ctDNA evaluable set or ctDES). The outcome will be assessed as the number of participants with a ≥ 3 fold decrease in ctDNA level, a number without dispersion.

  12 weeks

Secondary Outcomes (4)

• Presence of Detectable ctDNA Following Chemotherapy

  12 weeks

• Overall Survival (OS)

  2 years

• Progression free survival (PFS)

  2 years

• Durvalumab and Tremelimumab related Adverse Events (Cohort 1 MRD+ only)

  13 months

Study Arms (2)

Cohort 1 minimal residual disease positive (MRD+)

EXPERIMENTAL

Subjects with detectable ctDNA will receive 4 cycles of platinum doublet chemotherapy \[carboplatin/pemetrexed\], tremelimumab (75 mg IV every 21 days) and durvalumab (1500 mg IV every 21 days), except subjects with squamous cell carcinoma histology will receive carboplatin/paclitaxel. Subjects will be evaluated with PET/CT and/or computed tomography (CT) thorax every 12 weeks. Following ctDNA evaluation, in the absence of progression or toxicity, subject will continue with durvalumab to complete 1 year of treatment as standard of care.

Drug: Durvalumab; Drug: Carboplatin; Drug: Pemetrexed; Drug: Paclitaxel; Drug: Cisplatin; Device: AVENIO ctDNA Surveillance Kit; Drug: Tremelimumab

Cohort 2 minimal residual disease negative (MRD )

EXPERIMENTAL

Subjects with undetectable ctDNA at study enrollment will receive standard of care durvalumab (10 mg/kg every 2 weeks, or equivalent, for 1 year). If subjects in Cohort 2 MRD progress prior to close of study, blood will be drawn for ctDNA testing.

Drug: Durvalumab; Device: AVENIO ctDNA Surveillance Kit

Interventions

Durvalumab DRUG

Cohort 1 (1500 mg IV every 21 days, for 1 year), •Cohort 2 (10mg/kg every 2 weeks for 1 year)

Also known as: Imfinzi, MEDI-4736, MEDI4736

Cohort 1 minimal residual disease positive (MRD+); Cohort 2 minimal residual disease negative (MRD )

Carboplatin DRUG

Target area under the curve (AUC) not to exceed 750mg on Day 1 of every 21-day cycle

Also known as: Carboplat, Carbosol, Carboplatino, cis-diammine(cyclobutane-1,1-dicarboxylato)platinum

Cohort 1 minimal residual disease positive (MRD+)

Pemetrexed DRUG

500mg/m2 on Day 1 of every 21-day cycle

Also known as: Alimta, MTA, LY231514, L-glutamic acid, N-(4-(2-(2-Amino-4,7-dihydro-4-oxo-1H-pyrrolo(2,3-d)pyrimidin-5-yl)ethyl)benzoyl)

Cohort 1 minimal residual disease positive (MRD+)

Paclitaxel DRUG

175mg/m2 on Day 1 of every 21-day cycle

Also known as: Praxel

Cohort 1 minimal residual disease positive (MRD+)

Cisplatin DRUG

Cisplatin (75mg/m2 per institution guidelines) may be substituted for Carboplatin

Also known as: platinum diamminodichloride, Abiplatin, Cismaplat, cis-platinum, Platinex, platinum, diaminedichloro-, cis- (8CI)

Cohort 1 minimal residual disease positive (MRD+)

AVENIO ctDNA Surveillance Kit DEVICE

Roche Sequencing and Life Science kit to detect minimal residue disease (MRD)

Cohort 1 minimal residual disease positive (MRD+); Cohort 2 minimal residual disease negative (MRD )

Tremelimumab DRUG

not to exceed 75mg IV on Day 1 of every 21-day cycle

Also known as: Imjudo, Tremelimumab-actl, Ticilimumab, CP-675, CP-675,206

Cohort 1 minimal residual disease positive (MRD+)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically- or cytologically-documented NSCLC presenting with locally-advanced, unresectable stage III disease (Version 8 of AJCC Staging Manual) or NSCLC with locoregional recurrence after previous definitive treatment.
• For stage III or recurrent disease, must have completed platinum-based chemotherapy and radiation therapy to all known tumor sites (60 Gy +/- 10%). Must not have known progression of disease.
• Must be receiving consolidation durvalumab following completion of radiation and chemotherapy, and less than 32 weeks has elapsed from their first dose of durvalumab. (Patients may sign consent for study before start of durvalumab, but confirm eligibility and enroll only after first dose of durvalumab is received).
• Able to potentially receive further consolidation chemotherapy plus durvalumab and tremelimumab, but not be currently intended to receive additional systemic consolidation chemotherapy apart from this durvalumab.
• Pre-treatment tumor tissue or tumor DNA sample is believed to be available for analysis
• Aged 18 years or older
• Weight \> 30kg
• Life expectancy ≥ 12 weeks
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Absolute neutrophil count \> 1.0 x 109/L (1000/mm3)
• Platelets \> 75 x 109/L (100,000/mm3)
• Hemoglobin ≥ 9.0 g/dL (5.59 mmol/L)
• Measured creatinine clearance \> 40 mL/min, by either 24 hour urine collection or the Cockcroft Gault formula
• Males:
• Mass(kg) x (140-Age) / 72 x serum creatinine (mg/dL)

You may not qualify if:

• Involvement in the planning and/or conduct of the study
• \. Previous enrollment or randomization in the present study
• \. Received Investigational product as part of another clinical study
• \. Mixed small cell and non small cell lung cancer histology
• \. History of another primary malignancy and currently undergoing active treatment.
• Exception: May participate if receiving adjuvant endocrine therapy for breast or prostate cancer.
• \. Current or prior use of immunosuppressive medication within 14 days before enrollment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Systemic steroid administration required to manage toxicities arising from radiation therapy delivered as part of the chemoradiation therapy for locally advanced NSCLC is allowed.
• Subjects with Grade ≥ 2 neuropathy will be evaluated on a case by case basis after consultation with the Protocol Director / Principal Investigator
• Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by treatment with durvalumab may be included (ie, hearing loss) only after consultation with the Protocol Director / Principal Investigator.
• \. Any prior Grade ≥ 3 immune related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \> Grade 1) that may limit subject from continuing durvalumab during the study
• \. Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of study drug.
• \. Active or prior documented autoimmune or inflammatory disorders which is likely to limit the subjects ability to continue durvalumab on the study (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis; Graves' disease; rheumatoid arthritis; hypophysitis; uveitis; etc\]). Those with history of autoimmune or inflammatory disorders who are currently tolerating durvalumab may be eligible to participate with approval from the PI. The following are also exceptions to this criterion:
• Vitiligo or alopecia
• Hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
• Chronic skin condition not requiring systemic therapy

Sponsors & Collaborators

• Maximilian Diehn: lead
• AstraZeneca: collaborator

Study Sites (1)

Stanford University

Stanford, California, 94304, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab; Carboplatin; Pemetrexed; Glutamic Acid; Paclitaxel; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; tremelimumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Excitatory Amino Acids; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Maximilian Diehn, MD

  Stanford Universiy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rene Bonilla

CONTACT

650-498-7703; rbonilla@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Vice Chair of Research, Division Chief of Radiation and Cancer Biology

Study Record Dates

• First Submitted: October 6, 2020
• First Posted: October 14, 2020
• Study Start: August 25, 2021
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): April 1, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)