OT-101 in Combination With Atezolizumab for the Treatment of Metastatic or Recurrent Non-Small Cell Lung Cancer

NCT05935774 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: RG1123580NCI-2023-04564
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well trabedersen (OT-101) in combination with atezolizumab works in treating patients with non-small cell lung cancer (NSCLC) that has spread from where it first started (lung) to other places in the body (metastatic) or has come back after a period of improvement (recurrent). OT-101 is a transforming growth factor (TGF)-beta2 specific drug. TGF-beta2, a cytokine that is often overexpressed in various malignant tumors, may play an important role in promoting the growth, progression and migration of tumor cells. OT-101 binds to the TGF-beta2 receptor causing inhibition of protein production, thereby decreasing TGF-beta2 protein levels which may result in the inhibition of tumor cell growth and migration. Atezolizumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Giving OT-101 and atezolizumab together may be an effective treatment for patients with metastatic or recurrent NSCLC.

Conditions

Metastatic Lung Non-Small Cell Carcinoma; Recurrent Lung Non-Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Objective response measured by Response Evaluation Criteria in Solid Tumors version 1.1 defined as a confirmed or unconfirmed complete or partial response. Continuous outcomes will be summarized descriptively by means, medians, and quantiles. For the primary analyses, binary proportions will be estimated along with 90% confidence intervals.

  Up to 60 months

Secondary Outcomes (5)

• Duration of response

  From first documented response to progressive disease, symptomatic deterioration, or death due to any cause in responder subset, assessed up to 60 months

• Disease control rate

  At 6 months from treatment initiation

• Progression free survival

  Duration between treatment initiation and progressive disease, symptomatic deterioration, or death due to any cause, whichever occurs first, assessed up to 60 months

• Overall survival

  From the date of treatment initiation to date of death due to any cause, assessed up to 60 months

• Incidence of adverse events

  Up to 90 days

Study Arms (1)

Treatment (atezolizumab, trabedersen)

EXPERIMENTAL

Patients recieve atezolizumab IV on day 1 and trabedersen continuous IV on days 1-4 and days 15-19 of each cycle. Cycles repeat every 28 days for 104 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT or MRI during screening and every 8 weeks for the first 24 weeks and then every 12 weeks thereafter. Patients undergo blood sample collection prior to initiation of therapy, on day 4 of cycles 1-4, prior to weeks 4 and 8 of therapy, and at time of progression. Patients may also undergo biopsy during screening and/or 6-8 weeks after initiation of therapy.

Biological: Atezolizumab; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Other: Electronic Health Record Review; Procedure: Magnetic Resonance Imaging; Drug: Trabedersen (OT-101)

Interventions

Atezolizumab BIOLOGICAL

Given IV

Also known as: MPDL328OA, RG7446, RO5541267, Tecentriq

Treatment (atezolizumab, trabedersen)

Biopsy PROCEDURE

Undergo biopsy

Also known as: Bx

Treatment (atezolizumab, trabedersen)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection

Treatment (atezolizumab, trabedersen)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure)

Treatment (atezolizumab, trabedersen)

Electronic Health Record Review OTHER

Ancillary studies

Treatment (atezolizumab, trabedersen)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Treatment (atezolizumab, trabedersen)

Trabedersen (OT-101) DRUG

Given IV

Also known as: AP 12009

Treatment (atezolizumab, trabedersen)

Eligibility Criteria

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

You may qualify if:

• Participants aged 18 years and older
• Pathologically or cytologically confirmed non-small cell lung cancer with no known targetable genomic alterations with Food and Drug Administration (FDA) approved targeted therapies: including EGFR mutation, ALK rearrangement, ROS1 rearrangements MET or RET fusions, BRAF mutations, HER2 mutations or NTRK fusion
• Metastatic or recurrent NSCLC who have received prior immune checkpoint inhibitor and chemotherapy (in first or second line) for metastatic or recurrent disease and have had at least one prior line of cancer directed therapy
• Minimum duration on first-line immune checkpoint inhibitor (ICI) is 84 days (cannot have had progressive disease \[PD\] as best response)
• At least one site of measurable disease as determined by the Investigator, using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria. Participants must have measurable disease, defined as at least one lesion that can be measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral CT scan
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1. Participants must have ECOG PS 0 or 1 at the time of informed consent and at the time of treatment initiation
• NOTE: Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention
• Must be willing to provide pre-treatment archived specimen or undergo a biopsy procedure if archived specimen is not available or if \> 6 months old
• Must be willing to provide an on-treatment biopsy, if deemed safe by the treating physician. If deemed unsafe by the treating physician, the on-treatment biopsy requirement will be waived
• Platelet count \>= 100,000/uL
• Absolute neutrophil count \>= 1,500/uL
• Hemoglobin \>= 9g/dL (transfusions are allowed if done before 14 days of measurement)
• Serum albumin \>= 25 g/L (2.5 g/dL)
• For patients not receiving therapeutic anticoagulation: International normalized ratio (INR) or activated partial thromboplastin time (aPTT) =\< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 times upper limit of normal, in the presence of liver metastasis AST and ALT =\< 5 times upper limit of normal

You may not qualify if:

• Participants who have had chemotherapy or systemic therapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. NOTE: Participants must have recovered from all adverse events (AEs) due to previous therapies to =\< grade 1 or baseline. Participants with =\< grade 2 neuropathy are eligible. Participants with endocrine-related AEs grade =\< 2 requiring treatment or hormone replacement are eligible
• Patients for whom best response to 1 line (L ) or 2L treatment with was progressive disease within 84 days of treatment
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities and not have had radiation pneumonitis
• Surgery within 21 days of start of study treatment. Minor surgery within 2 weeks of start of study treatment. Placement of vascular access device and biopsies are not considered major or minor surgery and are allowed
• Has a history of a second invasive malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. All patients with previously treated in situ carcinoma are eligible, as patients with history of non-melanoma skin cancer
• Symptomatic central nervous system (CNS) metastases; participants with known brain metastasis must be asymptomatic with no steroids or antiepileptics within 7 days prior to start of study treatment
• Patients with untreated CNS metastases may be enrolled as long as they meet the above criteria. Patients with bulky CNS metastases should consider receiving radiation prior to study entry per investigator judgment
• Participants with spinal cord compression must have received local treatment and must have been symptomatically stable with no use of steroids for at least 7 days prior to start of study treatment
• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis, with the following exceptions:
• Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study
• Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:
• Rash must cover \< 10% of body surface area
• Disease is well controlled at baseline and requires only low-potency topical corticosteroids
• There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months
• Participants must not have an active autoimmune disease that has required immune modulating treatment within two years prior to consenting (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs)

Sponsors & Collaborators

• University of Washington: lead
• Genentech, Inc.: collaborator
• Oncotelic Therapeutics, Inc.: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

atezolizumab; Biopsy; Magnetic Resonance Spectroscopy; Trabedersen

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Rafael Santana-Davila

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 29, 2023
• First Posted: July 7, 2023
• Study Start: December 1, 2023
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: August 25, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)