Study of Durvalumab or Durvalumab Plus Chemotherapy in Kras Mutation Positive and PD-L1 High (≥ 50%) NSCLC Patients

NCT04470674 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: HCRN LUN17-126
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a two arm, randomized, phase II study of patients with advanced KRAS mutation positive and PD-L1 high NSCLC who have not received therapy for advanced stage disease. Patients will be randomized between Arm A and Arm B treatment. Arm A treatment will consist of durvalumab every 4 weeks for 13 cycles. Arm B treatment will consist of durvalumab with chemotherapy every 3 weeks for 4 cycles followed by durvalumab with pemetrexed every 3 weeks for 13 cycles.

Conditions

Lung Cancer; Non-small Cell Lung Cancer; PD-L1 Gene Mutation; KRAS Activating Mutation

Outcome Measures

Primary Outcomes (1)

• Response Rate

  Assess response rate by RECIST criteria 1.1 in Arm A and Arm B in advanced Kras mutation positive and PD-L1 high (≥50%) NSCLC patients.The objective response rate is the proportion of all subjects with confirmed PR or CR according to RECIST 1.1, from the start of treatment until disease progression/recurrence

  12 months

Secondary Outcomes (3)

• Progression Free Survival

  12 months

• Assess adverse events

  12 months

• Overall Survival

  12 months

Study Arms (2)

Arm A (Durvalumab)

ACTIVE COMPARATOR

Durvalumab 1500 mg IV every 4 weeks for 13 cycles.

Drug: Durvalumab

Arm B (Durvalumab plus chemotherapy)

EXPERIMENTAL

Durvalumab 1500 mg IV plus carboplatin AUC 5 IV and pemetrexed 500 mg/m2 IV every 3 weeks for 4 cycles followed by durvalumab and pemetrexed every 3 weeks for 13 more cycles.

Drug: Durvalumab; Drug: Carboplatin; Drug: Pemetrexed

Interventions

Durvalumab DRUG

Durvalumab 1500 mg

Also known as: IMFINZI

Arm A (Durvalumab); Arm B (Durvalumab plus chemotherapy)

Carboplatin DRUG

carboplatin AUC 5

Arm B (Durvalumab plus chemotherapy)

Pemetrexed DRUG

pemetrexed 500 mg/m2

Also known as: Alimta

Arm B (Durvalumab plus chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• Body weight \> 30 kg. If body weight falls to 30 kg or below during the study, the subject will be removed from study drugs.
• ECOG Performance Status of 0-1 within 7 days prior to registration.
• Life expectancy of ≥ 12 weeks.
• Histological or cytological evidence of stage IV Kras mutation positive non-squamous NSCLC.
• Patients who have recurrence following treatment for earlier stages of NSCLC are eligible provided the recurrence has not occurred within 12 months of completing prior therapy.
• Patient's tumor must be known to be PD-L1 high (≥ 50%). SP-142 assay will not be accepted. See Section 8.1 for additional information regarding this result.
• Measurable disease according to RECIST v1.1 criteria within 4 weeks of study registration.
• Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 14 days prior to registration.
• Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm3
• Hemoglobin (Hgb) ≥ 9.0 g/dL
• Platelets ≥ 75 k/mm3
• Calculated creatinine clearance ≥ 45 cc/min using the Cockcroft-Gault formula
• Bilirubin ≤ 1.5 × upper limit of normal (ULN) This will not apply to subjects with clinical diagnosis of Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology)

You may not qualify if:

• Patient must not have received any prior systemic therapy for stage IV NSCLC. Patients must not have received prior anti-PD-1 or anti-PD-L1.
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Testing is not required at screening.
• Patients with history of non-infectious pneumonitis that required steroids or has current pneumonitis. Has known history of Interstitial Lung Disease (ILD) or radiation pneumonitis which required therapy with steroids.
• Active or prior documented autoimmune or inflammatory (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]) and pneumonitis. The following are exceptions to this criterion:
• Diverticulosis
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study sponsor investigator.
• Patients with celiac disease controlled by diet alone
• History of allogenic progenitor/stem cell or organ transplantation.
• History of immunodeficiency. Patient should not be on any immunosuppressive therapy or steroids \> prednisone 10mg/day or its equivalent on the day of the start of therapy.
• Patients with current or prior use of immune suppressive therapy within 7 days of starting study therapy. Following exceptions are allowed
• Intranasal, local (eg. Intraarticular injections), inhaled or topical steroids
• Steroids to prevent hypersensitivity reactions, eg. IV contrast for CT scans

Sponsors & Collaborators

• Shirish M Gadgeel: lead
• AstraZeneca: collaborator
• Henry Ford Health System: collaborator

Study Sites (1)

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

durvalumab; Carboplatin; Pemetrexed

Condition Hierarchy (Ancestors)

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

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

Study Officials

• Shirish M Gadgeel, MBBS

  Henry Ford Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: July 9, 2020
• First Posted: July 14, 2020
• Study Start: April 6, 2021
• Primary Completion: June 8, 2021
• Study Completion: June 8, 2021
• Last Updated: March 3, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)