Pembrolizumab With or Without Anetumab Ravtansine in Treating Patients With Mesothelin-Positive Pleural Mesothelioma

NCT03126630 | Active Not Recruiting Phase 1 Results FDA Drug

• 5 other identifiers: NCI-2017-00633MC172110107UM1CA186686UM1CA186709
• Study Type: interventional
• Target: 49
• Locations: 2 countries
• Sites: 33

Brief Summary

This phase I/II trial studies the side effects and how well pembrolizumab with or without anetumab ravtansine works in treating patients with mesothelin-positive pleural mesothelioma. Anetumab ravtansine is a monoclonal antibody, called anetumab, linked to a chemotherapy drug, called ravtansine. Anetumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as mesothelin receptors, and delivers ravtansine to kill them. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving pembrolizumab and anetumab ravtansine may work better in treating patients with mesothelin-positive pleural mesothelioma.

Conditions

Pleural Malignant Mesothelioma

Outcome Measures

Primary Outcomes (2)

• Phase 2 Confirmed Tumor Response Rate (Phase II)

  Will be assessed using Response Evaluation Criteria in Solid Tumors version 1.1 criteria. The proportion of successes will be estimated in each group by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated in each arm. Comparison of confirmed response rates between the two treatment groups will be performed using a one-sided z-test with pooled variance at significance level 0.10. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  Up to 2 years

• Phase I - Recommended Phase 2 Dose of Ametumab Ravtansine With Combination of Pembrolizumab

  All patients that have received any amount of the combination anetumab ravtansine and pembrolizumab will be evaluable for toxicity. Please note this is different from the definition of evaluable for dose-limiting toxicity (DLT) where patients who cannot complete the planned dose due to reasons other than toxicity will be replaced.

  Up to 2 years

Secondary Outcomes (7)

• Phase 2 Duration of Response

  Up to 2 years

• Phase 2 Overall Survival

  From the start of treatment to death due to any cause, assessed up to 2 years

• Phase 2 Progression Free Survival

  From the start of treatment to the earliest date of documentation of disease progression or death due to any cause, assessed up to 2 years

• Pharmacokinetics of Anetumab Ravtansine

  Days 1 and 3 of courses 1 and 8

• Change in Megakaryocyte Potentiating Factor Levels Assessed in Tumor

  Baseline up to 2 years

Study Arms (2)

Group I (pembrolizumab)

ACTIVE COMPARATOR

Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. Upon radiologic documentation of disease progression, patients may cross over to Group II.

Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Other: Pharmacological Study

Group II (anetumab ravtansine, pembrolizumab)

EXPERIMENTAL

Patients receive anetumab ravtansine IV over 1 hour and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for up to 12 months for anetumab ravtansine and up to 24 months for pembrolizumab in the absence of disease progression or unacceptable toxicity.

Biological: Anetumab Ravtansine; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Other: Pharmacological Study

Interventions

Anetumab Ravtansine BIOLOGICAL

Given IV

Also known as: BAY 94-9343

Group II (anetumab ravtansine, pembrolizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Group I (pembrolizumab); Group II (anetumab ravtansine, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: BCD-201, GME 751, GME751, Keytruda, Lambrolizumab, MK 3475, MK-3475, MK3475, Pembrolizumab Biosimilar BCD-201, Pembrolizumab Biosimilar GME751, Pembrolizumab Biosimilar QL2107, Pembrolizumab Biosimilar RPH-075, Pembrolizumab Biosimilar SB27, QL2107, RPH 075, RPH-075, RPH075, SB 27, SB-27, SB27, SCH 900475, SCH-900475, SCH900475

Group I (pembrolizumab); Group II (anetumab ravtansine, pembrolizumab)

Pharmacological Study OTHER

Correlative studies

Group I (pembrolizumab); Group II (anetumab ravtansine, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• PRE-REGISTRATION
• Patients must have histologically or cytologically confirmed malignant pleural mesothelioma
• Patient is willing to submit a tissue sample to test for expression of mesothelin
• Note: Tissue sample for mesothelin assay may have been collected prior to, during or after receipt of the frontline chemotherapy; patients will not be required to submit another tissue sample after receipt of the chemotherapy
• Patients must have received platinum based chemotherapy
• REGISTRATION
• For phase 2 only:
• Patient has measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for non-pleural disease or modified RECIST 1.1 (mRECIST) for pleural disease
• Note: For pleural disease, this is defined as at least one lesion that can be accurately measured perpendicular to the chest wall or mediastinum that is \>= 10 mm (\>= 1 cm); for extra pleural disease, measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 10 mm (\>= 1 cm) for non-nodal lesions and \>= 15 mm (\>= 1.5 cm) for nodal lesions with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam as per RECIST 1.1
• Tissue submitted for testing at pre-registration shows moderate or stronger mesothelin expression in \>= 30% of the tumor cells
• For phase 1 and 2:
• Patients must have received platinum-based therapy with or without bevacizumab
• Eastern Cooperative Oncology Group (ECOG) performance status \< 2 (Karnofsky \>= 70%)
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL

You may not qualify if:

• Patients who have received any monoclonal antibody therapy within 4 weeks prior to entering the study
• Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1)
• Note: Patients with =\< grade 2 neuropathy or =\< grade 2 alopecia are an exception to this criterion and may qualify for the study
• Note: If patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• Patients who are receiving any other investigational agents
• Patients with known brain metastases with progressive neurologic dysfunction, requirement of steroids and lack of improvement on head imaging obtained prior to consent to this clinical trial should be excluded because of their poor prognosis and because they would confound the evaluation of neurologic and other adverse events
• Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging using the identical imaging modality for each assessment, either magnetic resonance imaging \[MRI\] or computed tomography \[CT\] scan, for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
• Note: Patients with carcinomatosis meningitis should also be excluded
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to anetumab ravtansine or pembrolizumab
• Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4, including herbal preparation containing CYP3A4 inducers (e.g., St. John's Wort), grapefruit and grapefruit juice (CYP3A4 inhibitor), within 2 weeks before the start of study treatment
• Patients are prohibited from receiving the following therapies during the screening and treatment phases (including retreatment for post-complete response relapse) of this trial:
• Antineoplastic systemic chemotherapy or biological therapy
• Immunotherapy not specified in this protocol
• Chemotherapy not specified in this protocol
• Investigational agents other than anetumab ravtansine and pembrolizumab

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (33)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

USC Norris Oncology/Hematology-Newport Beach

Newport Beach, California, 92663, United States

Location

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

UM Sylvester Comprehensive Cancer Center at Aventura

Aventura, Florida, 33180, United States

Location

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, 33146, United States

Location

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, 33442, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, 33176, United States

Location

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, 33324, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376, United States

Location

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

anetumab ravtansine; pembrolizumab

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Dr. Aaron Mansfield
• Organization: Mayo Clinic

mansfield.aaron@mayo.edu

(507) 284-2511

Study Officials

• Aaron S Mansfield

  Dana-Farber - Harvard Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2017
• First Posted: April 24, 2017
• Study Start: October 4, 2018
• Primary Completion: May 4, 2023
• Study Completion (Estimated): February 25, 2027
• Last Updated: April 1, 2026
• Results First Posted: October 16, 2024

Record last verified: 2026-02

Locations

CA (1); US (32)