Clinical Trials /

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

NCT04396340

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Non-Squamous Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: Mersana Therapeutics
  • NCT ID: NCT04396340

Conditions

  • Ovarian Cancer
  • Nonsmall Cell Lung Cancer

Interventions

DrugSynonymsArms
XMT-1592Confirmation of Dose

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalXMT-1592 is administered in groups of patients who will receive doses that increase over time until the maximum tolerated dose is achieved.
  • XMT-1592
Confirmation of DoseExperimentalNew groups of patients will receive XMT-1592 at the maximum tolerated dose to confirm the recommended Phase 2 dose
  • XMT-1592

Eligibility 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.
      
Maximum Eligible Age:95 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Evaluate adverse events and use of concomitant medication use after XMT-1592 doses

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Determine the pharmacokinetics of XMT-1592
Measure: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
Safety Issue:
Description:Determine the pharmacokinetics of XMT-1592
Measure: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
Safety Issue:
Description:Determine the pharmacokinetics of XMT-1592
Measure:Antineoplastic effects of XMT-1592
Time Frame:Every 6 weeks for up to 36 weeks
Safety Issue:
Description:Monitor tumor size
Measure:Anti-drug antibody and neutralizing antibody
Time Frame:Every 3 weeks for 9 weeks then every 6 weeks for upto 36 weeks
Safety Issue:
Description:Analyze blood for antibodies to XMT-1536 and neutralizing antibodies

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mersana Therapeutics

Last Updated

May 19, 2020