- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04396340
First-in-Human Study of XMT-1592 in Patients With Ovarian Cancer and NSCLC Likely to Express NaPi2b
March 14, 2024 updated by: Mersana Therapeutics
A Phase 1b, First-in-Human, Dose Escalation and Expansion Study of XMT-1592 In Patients With Solid Tumors Likely to Express NaPi2b
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.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
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
Interventional
Enrollment (Actual)
31
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Texas
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Dallas, Texas, United States, 75201
- Mary Crowley Cancer Research Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 95 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
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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.
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Experimental: Confirmation of Dose
New groups of patients will receive XMT-1592 at the maximum tolerated dose to confirm the recommended Phase 2 dose
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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Evaluate adverse events and use of concomitant medication use after XMT-1592 doses
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Up to 36 weeks, from the date of first dose until unacceptable side effects or a dose-limiting toxicity is me
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
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Determine the pharmacokinetics of XMT-1592
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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
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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
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Determine the pharmacokinetics of XMT-1592
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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
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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
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Determine the pharmacokinetics of XMT-1592
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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
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Antineoplastic effects of XMT-1592
Time Frame: Every 6 weeks for up to 36 weeks
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Monitor tumor size
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Every 6 weeks for up to 36 weeks
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Anti-drug antibody and neutralizing antibody
Time Frame: Every 3 weeks for 9 weeks then every 6 weeks for upto 36 weeks
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Analyze blood for antibodies to XMT-1536 and neutralizing antibodies
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Every 3 weeks for 9 weeks then every 6 weeks for upto 36 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Robert Burger, MD, Mersana Therapeutics
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 11, 2020
Primary Completion (Actual)
September 30, 2022
Study Completion (Actual)
September 30, 2022
Study Registration Dates
First Submitted
May 15, 2020
First Submitted That Met QC Criteria
May 15, 2020
First Posted (Actual)
May 20, 2020
Study Record Updates
Last Update Posted (Actual)
March 15, 2024
Last Update Submitted That Met QC Criteria
March 14, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lung Diseases
- Urogenital Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Genital Neoplasms, Female
- Endocrine System Diseases
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Endocrine Gland Neoplasms
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Carcinoma, Non-Small-Cell Lung
- Ovarian Neoplasms
- Carcinoma, Ovarian Epithelial
Other Study ID Numbers
- XMT-1592-1
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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