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First-in-Human Study of XMT-1592 in Patients With Ovarian Cancer and NSCLC Likely to Express NaPi2b

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ClinicalTrials.gov Identifier: NCT04396340
Recruitment Status : Recruiting
First Posted : May 20, 2020
Last Update Posted : May 12, 2021
Sponsor:
Collaborator:
IQVIA Biotech
Information provided by (Responsible Party):
Mersana Therapeutics

Brief Summary:
Phase 1b, a study in high grade serous ovarian cancer and nonsmall cell lung cancer to evaluate the safety and clinical activity of the antibody-drug conjugate (ADC) XMT-1592.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Nonsmall Cell Lung Cancer Biological: XMT-1592 Phase 1 Phase 2

Detailed Description:
This Phase 1b trial is an open-label, multi-center study of XMT-1592 administered as an intravenous infusion once every 3 weeks. The dose-escalation (DES) segment of the study will establish the expansion (EXP) dose and is intended to establish the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) for XMT-1592 in patients with high grade serous ovarian cancer (HGSOC) or non-small cell lung cancer (NSCLC), adenocarcinoma subtype. The EXP segment of the study will consist of 2 parallel cohorts of patients (HGSOC and NSCLC) to confirm the MTD or RP2D and estimate the objective response rate in each selected patient population. In DES, the observation period for dose-limiting toxicities is 21 days, between Day 1 through the end of Cycle 1 which includes the pre-dose assessments before receiving the Cycle 2 dose. All adverse events (AEs) will be graded according to NCI, CTCAE v5.0). In general, AEs ≥Grade 3 are dose-limiting toxicities with some modifications.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: Open-label, dose escalation to reach MTD. The MTD will be confirmed in 2 parallel cohorts: (1) patients with platinum-resistant ovarian cancer; (2) patients with non-squamous NSCLC, adenocarcinoma subtype.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b, First-in-Human, Dose Escalation and Expansion Study of XMT-1592 In Patients With Solid Tumors Likely to Express NaPi2b
Actual Study Start Date : May 11, 2020
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : June 2023


Arm Intervention/treatment
Experimental: Dose Escalation
XMT-1592 is administered in groups of patients who will receive doses that increase over time until the maximum tolerated dose is achieved.
Biological: XMT-1592
XMT-1592 will be administered once every 21 days until disease progression, unacceptable toxicity, or either the patient or study physician determines it is in the best interest of the patient to discontinue participation in the study.

Experimental: Confirmation of Dose
New groups of patients will receive XMT-1592 at the maximum tolerated dose to confirm the recommended Phase 2 dose
Biological: XMT-1592
XMT-1592 will be administered once every 21 days until disease progression, unacceptable toxicity, or either the patient or study physician determines it is in the best interest of the patient to discontinue participation in the study.




Primary Outcome Measures :
  1. Maximum tolerated dose or recommended Phase 2 dose [ Time Frame: Up to 36 weeks, from the date of first dose until unacceptable side effects or a dose-limiting toxicity is me ]
    Evaluate adverse events and use of concomitant medication use after XMT-1592 doses


Secondary Outcome Measures :
  1. Time of maximum observed concentration of XMT-1592 [ Time Frame: Daily for one week after first dose; weekly until 21 days after first dose; immediately before and after and 1 week after all subsequent doses ]
    Determine the pharmacokinetics of XMT-1592

  2. Maximum concentration of XMT-1592 [ Time Frame: Daily for one week after first dose; weekly until 21 days after first dose; immediately before and after and 1 week after all subsequent doses ]
    Determine the pharmacokinetics of XMT-1592

  3. Area under the concentration curve of the last measurable concentration of XMT-1592 [ Time Frame: Daily for one week after first dose; weekly until 21 days after first dose; immediately before and after and 1 week after all subsequent doses ]
    Determine the pharmacokinetics of XMT-1592

  4. Antineoplastic effects of XMT-1592 [ Time Frame: Every 6 weeks for up to 36 weeks ]
    Monitor tumor size

  5. Anti-drug antibody and neutralizing antibody [ Time Frame: Every 3 weeks for 9 weeks then every 6 weeks for upto 36 weeks ]
    Analyze blood for antibodies to XMT-1536 and neutralizing antibodies



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 95 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ability to give informed consent.
  • ECOG performance status 0 or 1.
  • Measurable disease as per RECIST, version 1.1. Resolution of all acute toxic effects of prior therapy or surgical procedures to Grade ≤1 (except alopecia).
  • Adequate organ function.
  • Confirmed availability of tumor tissue blocks or freshly cut tissue slides for NaPi2b testing. -In EXP, ability to undergo a fresh biopsy before enrollment, unless not medically feasible.
  • For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective form of hormonal contraception or two effective forms of non-hormonal contraception by the patient and/or partner, and to continue the use of contraception for the duration of study treatment and for at least 6 months after the last dose of study treatment.
  • Histologically or cytologically confirmed solid tumors of the types specified below, with incurable, locally advanced or metastatic disease that has failed standard therapy or for which no standard treatment option exists.
  • Ovarian Cancer: Histological diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer, excluding the mucinous subtype.

NSCLC: Histological diagnosis of nonsquamous NSCLC.

Exclusion Criteria:

  • Major surgery within 28 days of starting study treatment; -or- systemic anti-cancer therapy within the lesser of 28 days or 5 half-lives of the prior therapy before starting study treatment -or- recent radiation therapy with unresolved toxicity.
  • Brain metastases that are: untreated, progressive, have required any type of major treatment, e.g., whole-brain radiation treatment, adjuvant chemotherapy, gamma knife, to control symptoms from brain metastases within 30 days of the first study treatment. Or any history of leptomeningeal metastasis.
  • Current known active infection with HIV, hepatitis B virus, or hepatitis C virus.
  • No prior history of liver disease such as liver cirrhosis, hepatic fibrosis
  • Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) or intercurrent illness that could interfere with per-protocol evaluations.
  • Severe dyspnea at rest due to complications of advanced malignancy, or requiring supplementary oxygen therapy.
  • Currently active pneumonitis or interstitial lung disease.
  • Pregnant or nursing women.
  • History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.
  • Participation in the DES component of the study.
  • Prior use of mirvetuximab soravtansine or another ADC containing an auristatin or maytansinoid payload.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04396340


Contacts
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Contact: Leigh Keating, MS, RD 617-498-0020 lkeating@mersana.com

Locations
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United States, Michigan
Henry Ford Medical Center Recruiting
Detroit, Michigan, United States, 48235
Contact: LaToya Allen    313-916-9826      
Principal Investigator: Ding Wang, MD         
START Midwest Recruiting
Grand Rapids, Michigan, United States, 49545
Contact: Kathy Estkowski    616-954-5551      
Principal Investigator: Nehal Lakhani, MD         
United States, Pennsylvania
University of Pittsburgh Medical Center Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact       phase1@upmc.edu   
Principal Investigator: Timothy Burns, MD         
United States, Tennessee
Sarah Cannon Research Institute (SCRI) Recruiting
Nashville, Tennessee, United States, 37203
Contact: Research Nurse    615-339-4214      
Principal Investigator: Erika Hamilton, MD         
United States, Texas
Mary Crowley Cancer Research Center Recruiting
Dallas, Texas, United States, 75201
Contact: Timothy Eamma    214-658-1962      
Principal Investigator: Minal Barve, MD         
South Texas Accelerated Research Therapeutics (START) Recruiting
San Antonio, Texas, United States, 78229
Contact: Lauryn Tuckett    210-593-5242      
Principal Investigator: Kyri Papadopoulos, MD         
NEXT Oncology Recruiting
San Antonio, Texas, United States, 78240
Contact: Cynthia De Leon    210-580-9521      
Principal Investigator: Anthony Tolcher, MD         
Sponsors and Collaborators
Mersana Therapeutics
IQVIA Biotech
Investigators
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Study Director: Arvin Yang, MD, PhD Mersana Therapeutics
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Responsible Party: Mersana Therapeutics
ClinicalTrials.gov Identifier: NCT04396340    
Other Study ID Numbers: XMT-1592-1
First Posted: May 20, 2020    Key Record Dates
Last Update Posted: May 12, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Carcinoma, Non-Small-Cell Lung
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases