Anetumab Ravtansine and Atezolizumab in Treating Participants With Advanced Non-small Cell Lung Cancer

NCT03455556 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: MC1711NCI-2018-00307
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 3

Brief Summary

This phase I/II trial studies the best dose and side effects of anetumab ravtansine when given together with atezolizumab and how well they work in treating participants with non-small cell lung cancer that has spread to other places in the body. Monoclonal antibodies, such as anetumab ravtansine and atezolizumab, may interfere with the ability of tumor cells to grow and spread.

Conditions

Mesothelin Positive; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IV Non-Small Cell Lung Cancer AJCC v7

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) (Phase I)

  Maximum tolerated dose (MTD) of anetumab ravtansine combined with atezolizumab defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (Phase I)

  Up to 21 days

• Rate of Confirmed Response (Phase II)

  Defined as a patient who has achieved a partial response (PR) or complete response (CR) on two consecutive evaluations at least 4 weeks apart. Will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated.

  6 months

Secondary Outcomes (4)

• Clinical Activity (Phase I)

  Up to 6 months

• Incidence of Adverse Events According to Common Terminology Criteria for Adverse Events Version 4.0 (Phase I)

  Up to 21 days after last dose

• Overall Survival (Phase II)

  Up to 2 years

• Progression-free Survival (Phase II)

  1 year and up to 2 years

Study Arms (1)

Treatment (anetumab ravtansine, atezolizumab)

EXPERIMENTAL

Participants receive anetumab ravtansine IV over 60 minutes and atezolizumab IV over 30-60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Biological: Anetumab Ravtansine; Biological: Atezolizumab; Other: Laboratory Biomarker Analysis

Interventions

Anetumab Ravtansine BIOLOGICAL

Given IV

Also known as: BAY 94-9343

Treatment (anetumab ravtansine, atezolizumab)

Atezolizumab BIOLOGICAL

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Treatment (anetumab ravtansine, atezolizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (anetumab ravtansine, atezolizumab)

Eligibility Criteria

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

You may qualify if:

• Phase I only: Diagnosis of advanced/metastatic NSCLC for which no standard treatment option; Phase II only: Advanced NSCLC patients who have received at least 1 platinum-based systemic chemotherapy regimen
• Patients with tumors having actionable genomic alterations should have received prior therapy with Food and Drug Administration (FDA) approved agents targeting these aberrations (ie EGFR, ALK, ROS1, BRAF V600E)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Phase II only: Must have at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• Ability to understand and the willingness to sign a written informed consent document
• Histological or cytologically confirmed NSCLC that shows moderate or stronger mesothelin expression in 30% of tumor cells by a companion assay; MSLN expression score using Ventana immunohistochemistry (IHC) SP74 assay; Phase I only: In addition 5- 30% tumor cells and 1, 2, or 3+ MSLN score; Phase II only: 30% tumor cells and either 2+/3+
• Life expectancy of \>= 12 weeks
• Absolute neutrophil count \>= 1.5 ? 10\^9/L =\< 14 days prior to registration
• Platelets \>= 100 ? 10\^9/L =\< 14 days prior to registration
• Hemoglobin \>= 9 g/dL =\< 14 days prior to registration
• Potassium \>= lower limit of normal (LLN) range for the institution =\< 14 days prior to registration
• NOTE: Supplementation may be given before the first dose of study medication
• Calcium \>= LLN (corrected for serum albumin, if albumin abnormal) =\< 14 days prior to registration
• NOTE: Supplementation may be given before the first dose of study medication
• Magnesium \>= LLN =\< 14 days prior to registration

You may not qualify if:

• Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
• Note:
• Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:
• Minimum of 12 weeks from the first dose of anti-CTLA-4 and \> 6 weeks from the last dose
• No history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] grade 3 and 4)
• More than one prior taxane regimen at any stage of the disease under study (?taxane? refers to paclitaxel, docetaxel, abraxane and cabazitaxel); adjuvant and/or neoadjuvant treatments are considered together as one prior regimen
• Treatment with any other investigational agent or investigational device within 4 weeks prior to registration (or within five half-lives of the investigational product, whichever is longer); patients must be \>= 2 weeks since any investigational agent administered as part of a phase 0 study (also referred to as an ?early phase I study? or ?pre phase I study? where a sub- therapeutic dose of drug is administered) at the coordinating center principal investigator (PI)?s discretion, and should have recovered to eligibility levels from any toxicities
• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon-alpha or interleukin-2) within 6 weeks or five half-lives of the drug (whichever is shorter) prior to registration
• Received radiotherapy =\< 4 weeks or limited field radiation for palliation =\< 2 weeks prior to registration, and who has not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia) and/or in whom \>= 25 percent (%) of the bone marrow was irradiated
• Patients who have a previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study, except
• Cervical carcinoma in situ, non-melanoma skin cancer, superficial noninvasive bladder tumors, ductal carcinoma in situ (DCIS) or any previous cancer curatively treated \>3 years before the start of anetumab ravtansine
• Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) =\< 2 weeks prior to registration
• Note:
• Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled
• The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic Hospital

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

anetumab ravtansine; atezolizumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Alex A Adjei, MD, PhD
• Organization: Mayo Clinic

Adjei.Alex@mayo.edu

(507) 284-2511

Study Officials

• Alex Adjei

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2018
• First Posted: March 6, 2018
• Study Start: August 10, 2018
• Primary Completion: September 11, 2019
• Study Completion: January 7, 2020
• Last Updated: January 6, 2023
• Results First Posted: May 15, 2020

Record last verified: 2020-02

Locations

US (3)