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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04396340
Recruitment Status : Active, not recruiting
First Posted : May 20, 2020
Last Update Posted : August 30, 2022
Sponsor:
Collaborator:
IQVIA Biotech
Information provided by (Responsible Party):
Mersana Therapeutics

Tracking Information
First Submitted Date  ICMJE May 15, 2020
First Posted Date  ICMJE May 20, 2020
Last Update Posted Date August 30, 2022
Actual Study Start Date  ICMJE May 11, 2020
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 15, 2020)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 15, 2020)
  • 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
  • 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
  • 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
  • Antineoplastic effects of XMT-1592 [ Time Frame: Every 6 weeks for up to 36 weeks ]
    Monitor tumor size
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE First-in-Human Study of XMT-1592 in Patients With Ovarian Cancer and NSCLC Likely to Express NaPi2b
Official Title  ICMJE A Phase 1b, First-in-Human, Dose Escalation and Expansion Study of XMT-1592 In Patients With Solid Tumors Likely to Express NaPi2b
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • Ovarian Cancer
  • Nonsmall Cell Lung Cancer
Intervention  ICMJE Biological: XMT-1592
XMT-1592 will be administered once every 21 or 28 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.
Study Arms  ICMJE
  • 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.
    Intervention: Biological: XMT-1592
  • Experimental: Confirmation of Dose
    New groups of patients will receive XMT-1592 at the maximum tolerated dose to confirm the recommended Phase 2 dose
    Intervention: Biological: XMT-1592
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: May 15, 2020)
120
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2023
Estimated Primary Completion Date December 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 95 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04396340
Other Study ID Numbers  ICMJE XMT-1592-1
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Mersana Therapeutics
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Mersana Therapeutics
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE IQVIA Biotech
Investigators  ICMJE
Study Director: Ellie Im, MD Mersana Therapeutics
PRS Account Mersana Therapeutics
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP