Evaluating the Efficacy of Atezolizumab in Advanced Non-small Cell Lung Cancer (NSCLC)

NCT03014648 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HCC 16-153
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

Brief Summary

This is a phase II clinical trial aimed at evaluating the efficacy of PD-L1 inhibition with atezolizumab in advanced squamous and non-squamous NSCLC patients previously treated with anti-PD-1 therapy with either nivolumab or pembrolizumab. In order to account for the variability of response kinetics to PD-1 directed therapy, patients will be enrolled in 3 parallel cohorts based on the best overall response to PD-1 directed therapy.

• Cohort 1 (progressive disease)
• Cohort 2 (stable disease with minimum 12 weeks of therapy)
• Cohort 3 (partial to complete response followed by progressive disease)

Conditions

Advanced Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Best Overall Response (BOR)

  Best response recorded is recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Per RECIST v1.1: Complete Response (CR) - Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to \<10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Approximately 53.5 months

Secondary Outcomes (10)

• Duration of Response (DOR)

  Approximately 56.5 months

• Progression-free Survival (PFS)

  Approximately 56.5 months

• 6-month Progression-free Survival (PFS)

  Up to 6 months

• 12-month Progression-free Survival (PFS)

  Up to 12 months

• 24-month Progression-free Survival (PFS)

  Up to 24 months

Other Outcomes (1)

• PD-L1 Expression

  Up to 6 years

Study Arms (1)

Atezolizumab

EXPERIMENTAL

Atezolizumab will be given on day 1 of a 21-day cycle at 1200 mg IV over 60 (plus or minus 15) minutes for first infusion; can be decreased to 30 (plus or minus 10) minutes for subsequent cycles. Atezolizumab will be given as long as the patient continues to experience clinical benefit in the opinion of the investigator or until unacceptable toxicity, symptomatic deterioration attributed to disease progression. There will be no dose reduction for Atezolizumab. Patients may temporarily suspend study treatment for up to 84 days beyond the scheduled date of delayed infusion if study drug-related toxicity requiring dose suspension is experienced. If Atezolizumab is held because of adverse events for greater than 84 days beyond the scheduled date of infusion, the patient will be discontinued from Atezolizumab and will be followed for safety and efficacy.

Drug: Atezolizumab

Interventions

Atezolizumab DRUG

Atezolizumab will be administered through an IV over 60 minutes at a dose of 1200mg on Day 1 of each 21-day cycle. If the first dose is tolerated without any infusion-related adverse events, the following doses can be administered over 30 minutes.

Also known as: Tecentriq

Atezolizumab

Eligibility Criteria

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

You may qualify if:

• Patients with Stage IIIB/IV squamous or non-squamous NSCLC (American Joint Committee on Cancer 7th Edition Staging) who have had prior treatment with nivolumab or pembrolizumab will be enrolled in one of 3 parallel cohorts based on the following:
• Cohort 1: Patient with progressive disease on nivolumab or pembrolizumab as the best overall response. Progressive disease must be confirmed with a confirmatory scan ≤ 4 weeks after the 1st documented date of progression.
• Cohort 2: Patients with stable disease as the best overall response on a minimum of 12 weeks of therapy with nivolumab or pembrolizumab.
• Cohort 3: Patients with partial or complete response as the best overall response followed by progressive disease, on nivolumab or pembrolizumab. A confirmatory scan at the time of disease progression must be performed ≤ 4 weeks after the 1st documented date of progression.
• Both men and women of all races and ethnic groups are eligible for this trial
• Patients must have resolution of toxic effects to Grade 1 or less from prior therapy (except alopecia).
• Patients must sign Informed Consent Form and show ability and willingness to comply with the requirements of the study protocol.
• years of age or older
• Willingness to undergo a biopsy ≤ 6 weeks of the start of study treatment to obtain formalin-fixed paraffin-embedded tumor specimens in paraffin blocks (blocks are preferred) or at least 15 unstained slides, with an associated pathology report, for central testing of tumor PD-L1 expression.
• Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1):
• ANC equal to/greater than 1500 cells/µL
• WBC counts greater than 2500/µL
• Lymphocyte count equal to/greater than 300µ/L
• Platelet count equal to/greater than 100,000/µL
• Hemoglobin equal to/greater than 9.0 g/dL

You may not qualify if:

• Any approved anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment; however, the following are allowed:
• Hormone-replacement therapy or oral contraceptives.
• Herbal therapy greater than 1 week prior to Cycle 1, Day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to Cycle 1, Day 1).
• Hormonal therapy for prostate cancer or breast cancer provided criteria in 3.2.21 are met.
• Palliative radiotherapy (e.g., treatment of known bony metastases) allowed, provided it does not interfere with the assessment of tumor target lesions (e.g. the lesion being irradiated is not the only site of disease, because that would render the patient not evaluable for response by tumor assessments according to RECIST v1.1).
• Adverse events from prior anticancer therapy that have not resolved to Grade equal to/less than1 except for alopecia.
• History of grade 4 immune-related adverse events requiring treatment with prednisone or history of grade 3 immune-related adverse events requiring prednisone \>10 mg/kg for \>12 weeks.
• Bisphosphonate therapy for symptomatic hypercalcemia (use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed).
• Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease.
• Patients with acute leukemias, accelerated/blast phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma.
• Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases. Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:
• Evaluable or measurable disease outside the CNS.
• No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm).
• No history of intracranial hemorrhage or spinal cord hemorrhage.
• No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted.

Sponsors & Collaborators

• Liza Villaruz, MD: lead
• Genentech, Inc.: collaborator

Study Sites (2)

AdventHealth Orlando

Orlando, Florida, 32804, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Interventions

atezolizumab

Results Point of Contact

• Title: Barbara M Stadterman, Regulatory Supervisor, Clinical Research Services
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

412-647-5554

Study Officials

• Liza Villaruz, MD

  University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: December 29, 2016
• First Posted: January 9, 2017
• Study Start: July 18, 2017
• Primary Completion: December 31, 2021
• Study Completion: March 31, 2022
• Last Updated: December 13, 2023
• Results First Posted: December 13, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)