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

Phase 1 Safety Run-In and Phase 2 Randomized Clinical Trial of Anetumab Ravtansine and Pembrolizumab (MK-3475) Compared to Pembrolizumab Alone for Mesothelin-Positive Malignant Pleural Mesothelioma

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pleural Malignant Mesothelioma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Biological: Pembrolizumab; Biological: Anetumab Ravtansine

Detailed Description

PRIMARY OBJECTIVES:

I. Determine the dose of anetumab ravtansine that is safe in combination with pembrolizumab to be used in the randomized phase 2 study. (Phase I safety lead-in) II. Determine if the overall response rate of the combination of anetumab ravtansine and pembrolizumab is superior to pembrolizumab alone. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the progression free survival of anetumab ravtansine and pembrolizumab compared to pembrolizumab alone.

II. To evaluate the pharmacodynamic effects of anetumab ravtansine and pembrolizumab on soluble megakaryocyte potentiating factor (MPF).

III. To evaluate the pharmacokinetics of anetumab ravtansine and pembrolizumab. IV. To evaluate mononuclear phagocyte system (MPS) function, FcgammaRs, hormone and chemokine mediators as methods to evaluate factors affecting the pharmacokinetics and pharmacodynamics of these agents.

V. To determine the incidence of antibodies directed against anetumab ravtansine.

CORRELATIVE STUDY OBJECTIVES:

I. To determine whether elevations in Bim in tumor-reactive T cells (TTR) predict responses to treatment and whether its detection is dynamic with treatment.

II. To determine whether soluble PD-L1 predicts responses to treatment and whether its detection is dynamic with treatment.

III. To evaluate PD-L1 expression in archival tissue as a predictive marker of response to pembrolizumab-based therapy.

IV. To explore the symptomatic adverse events (AE) for tolerability of each treatment group using Patient Reported Outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE).

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients receive pembrolizumab intravenously (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.

GROUP II: 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.

After completion of study treatment, patients are followed up for 12 months.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital in Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90033
      • USC / Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90033
      • Los Angeles General Medical Center
    • Newport Beach, California, United States, 92663
      • USC Norris Oncology/Hematology-Newport Beach
  • Colorado
    • Aurora, Colorado, United States, 80045
      • UCHealth University of Colorado Hospital
  • Florida
    • Aventura, Florida, United States, 33180
      • UM Sylvester Comprehensive Cancer Center at Aventura
    • Coral Gables, Florida, United States, 33146
      • UM Sylvester Comprehensive Cancer Center at Coral Gables
    • Deerfield Beach, Florida, United States, 33442
      • UM Sylvester Comprehensive Cancer Center at Deerfield Beach
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine-Sylvester Cancer Center
    • Miami, Florida, United States, 33176
      • UM Sylvester Comprehensive Cancer Center at Kendall
    • Plantation, Florida, United States, 33324
      • UM Sylvester Comprehensive Cancer Center at Plantation
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky/Markey Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center at West County Hospital
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63129
      • Siteman Cancer Center-South County
    • Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center at Saint Peters Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute (UPCI)
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern/Simmons Cancer Center-Dallas
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
• Platelets >= 100,000/mcL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN)
• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN AND partial thromboplastin time (PTT) or activated PTT (aPTT) =< 1.5 x ULN, unless patient is on stable dose of anti-coagulation therapy in which case patients will be allowed to participate if they have no signs of bleeding or clotting and the INR/PT and PTT/aPTT results are compatible with an acceptable risk-benefit ratio as per the investigator's discretion

• Negative serum pregnancy test for females of child bearing potential

  • Note: Females are considered to not be of child bearing potential if any of the following apply:
  • Postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women < 45 years of age, a high follicle stimulating hormone [FSH] level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient);
  • Have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening;
  • Has a congenital or acquired condition that prevents childbearing

• Patient agrees to use one of the following acceptable methods of contraception prior to study entry, during study participation, and for at least six months after receiving the last dose of study treatment:

  • Acceptable methods of contraception are:

    • Single method (1 of the following is acceptable):

      • Abstinence, if consistently employed as the patient's preferred and usual lifestyle and if considered acceptable by local regulatory agencies and Institutional Review Boards (IRBs)
      • Intrauterine device (IUD)
      • Vasectomy of a female patient's male partner
      • Contraceptive rod implanted into the skin

    • Combination method (requires use of 2 of the following):

      • Diaphragm with spermicide (cannot be used in conjunction with cervical cap/spermicide)
      • Cervical cap with spermicide (nulliparous women only)
      • Contraceptive sponge (nulliparous women only)
      • Male condom or female condom (cannot be used together)
      • Hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or progestin-only pill), contraceptive skin patch, vaginal contraceptive ring, or subcutaneous contraceptive injection
• Ability to understand and the willingness to sign a written informed consent document, unless patient is of impaired decision making capacity in which case patient may be eligible if they have a legal authorized representative or caretaker available

Exclusion Criteria:

• 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
  • Radiation therapy (Note: Radiation therapy to a symptomatic solitary lesion or to the brain may be considered on an exceptional case by case basis after consultation with Cancer Therapy Evaluation Program (CTEP); the patient must have clear measurable disease outside the radiated field; administration of palliative radiation therapy will be considered clinical progression for the purposes of determining progression free survival [PFS])
  • Live vaccines within 30 days prior to the first dose of trial treatment and while participating in the trial; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Chalmette-Guerin (BCG), and typhoid (oral) vaccine; seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
  • Systemic glucocorticoids for any purpose other than to modulate symptoms from an event of suspected immunologic etiology; the use of physiologic doses of corticosteroids may be approved after consultation with the study principal investigator (PI) and CTEP
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Women who are pregnant or breastfeeding.

  • Note: Pregnant women are excluded from this study because anetumab ravtansine and pembrolizumab are agents with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with anetumab ravtansine and pembrolizumab, breastfeeding should be discontinued if the mother is treated with anetumab ravtansine or pembrolizumab

• Human immunodeficiency virus (HIV)-positive patients who do not meet all of the following and/or are on HIV medications considered to be strong inhibitors or inducers of CYP3A4:

  • Undetectable HIV viral load by standard clinical assay within 6 months of registration
  • Willing to adhere to antiretroviral therapy that has minimal overlapping toxicity or pharmacokinetic interactions with protocol therapy
  • No acquired immunodeficiency syndrome (AIDS)-defining events other within the past 12 months
  • Near normal life expectancy if not for the presence of the cancer

• Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid [RNA] [qualitative] is detected) infection

  • Note: No testing for hepatitis B and hepatitis C is required unless mandated by local health authority
• Patients who are known to have a history of or a finding of corneal epitheliopathy at pre-study are excluded because anetumab ravtansine may worsen this condition and reduce vision
• Known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cervical cancer
• Receipt of transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony-stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF], or recombinant erythropoietin) within 4 weeks prior to study treatment
• Patient with active interstitial lung disease (ILD)/pneumonitis or a prior history of ILD/pneumonitis requiring treatment with steroids
• Patient has received prior treatment with PD-1, PD-L1 or PD-L2 inhibitor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group I (pembrolizumab); 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; Correlative studies; Other: Pharmacological Study; Correlative studies; Biological: Pembrolizumab; Given IV; Other Names: Keytruda; MK-3475; Lambrolizumab; SCH 900475; BCD-201; Pembrolizumab Biosimilar BCD-201
Experimental: Group II (anetumab ravtansine, pembrolizumab); 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Biological: Pembrolizumab; Given IV; Other Names: Keytruda; MK-3475; Lambrolizumab; SCH 900475; BCD-201; Pembrolizumab Biosimilar BCD-201; Biological: Anetumab Ravtansine; Given IV; Other Names: BAY 94-9343

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended phase 2 dose of anetumab ravtansine with combination of pembrolizumab	An early safety analysis will be performed after the first 6 patients have been accrued to the safety lead-in portion of the study at dose level 1 and observed for one cycle. If 2 or more of the first 6 patients experience a dose limiting toxicities, then the starting dose level will be adjusted and additional cohorts may be evaluated. All patients that have received any amount of the combination anetumab ravtansine and pembrolizumab will be evaluable for toxicity.	Up to 21 days
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.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response	Will be defined as evaluable patients who achieved noted to be a partial response or complete response based Response Evaluation Criteria in Solid Tumors version 1.1 criteria. Will be estimated using the method of Kaplan-Meier. The comparison of duration of response between two treatment arms will be based on the log-rank test. This calculation will start with the date of start of treatment.	Up to 2 years
Overall survival	Will be estimated using the method of Kaplan-Meier. The comparison of overall survival between two treatment arms will be based on the log-rank test.	From the start of treatment to death due to any cause, assessed up to 2 years
Progression free survival	Will be estimated using the method of Kaplan-Meier. The comparison of progression-free survival between two treatment arms will be based on the log-rank test.	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
Incidence of adverse events	Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed for each arm to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration. The overall adverse event rates for grade 3 or higher hematologic and non-hematologic adverse events at least possibly related to treatment will be compared between the two treatment groups using the Chi-square test (or Fisher's exact test if the data in the contingency table is sparse).	Up to 30 days after last dose of study drug
Pharmacokinetics of anetumab ravtansine	Will be largely descriptive. Changes over time will be plotted and assessed for each patient.	Days 1 and 3 of courses 1 and 8
Change in megakaryocyte potentiating factor levels assessed in tumor	Relative changes in biomarker levels will be compared by best overall response groups using the non-parametric Wilcoxon rank-sum test. Also, the associations between changes in megakaryocyte potentiating factor levels and ordered response categories (i.e. complete response-partial response-stable disease-progressive disease) will be assessed with the Jonckheere-Terpstra test for trend.	Baseline up to 2 years
Mononuclear phagocyte system -FcgammaRs and chemokine mediators of mononuclear phagocyte system	The mean equivalent soluble fluorophore and antibody bound to cell (ABC) will be determined for each specimen. Linear regression will be used to explore the linear relationship between the continuous values of these mononuclear phagocyte system-FcgammaRs probes and anetumab ravtansine levels. The concentrations of CCL2 and CCL5 will be determined for each specimen. Linear regression will be used to explore the linear relationship between the continuous values of these chemokines and anetumab ravtansine levels.	Up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurements of Bim in tumor-reactive T cells (TTR)	Measurements of Bim in TTR as a predictor of responses to treatment. Is anticipated that a non-parametric test such as the Mann-Whitney test should be used to compare Bim in TTR between subjects that do and do not respond to therapy.	Up to 2 years
Measurements of soluble PD-L1	Measurements of soluble PD-L1 as a predictor of responses to treatment. Is anticipated that a non-parametric test such as the Mann-Whitney test should be used to compare soluble PD-L1 between subjects that do and do not respond to therapy.	Up to 2 years
PD-L1 expression in archival tissue	PD-L1 expression in archival tissue as a predictive marker of response to pembrolizumab-based therapy. Will compare whether there is a difference in the number of responders with 50% or greater PD-L1 tumor cell expression and those without with the Chi-square test (or Fisher's exact test if the data in the contingency table is sparse).	Up to 2 years
Patient reported outcomes-Common Terminology Criteria for Adverse Events		Up to 2 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Aaron S Mansfield, Dana-Farber - Harvard Cancer Center LAO

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2018
• Primary Completion (Actual): July 8, 2023
• Study Completion (Estimated): September 21, 2024

Study Registration Dates

• First Submitted: April 20, 2017
• First Submitted That Met QC Criteria: April 20, 2017
• First Posted (Actual): April 24, 2017

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Mesothelioma; Mesothelioma, Malignant; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Immunoconjugates; Pembrolizumab; Maytansine; Anetumab ravtansine
• Other Study ID Numbers: NCI-2017-00633 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); UM1CA186709 (U.S. NIH Grant/Contract); UM1CA186686 (U.S. NIH Grant/Contract); MC1721; 10107 (Other Identifier: CTEP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No