Clinical Trials /

First-in-Human Study of XMT-1536 in Cancers Likely to Express NaPi2b

NCT03319628

Description:

First-in-human, Phase 1b safety study of the antibody-drug conjugate (ADC) XMT-1536 administered as an intravenous infusion once every four weeks. Patients with tumor types likely to express NaPi2b were enrolled in dose escalation. Patients with platinum-resistant ovarian cancer and non-small cell lung cancer (adenocarcinoma subtype) are being enrolled in the expansion segment of this study. In addition to safety assessments, the pharmacokinetics of the drug will be assessed along with ADC activity.

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First-in-Human Study of XMT-1536 in Cancers Likely to Express NaPi2b
  • Official Title: A Phase 1b, First-in-Human, Dose Escalation and Expansion Study of XMT-1536 In Patients With Solid Tumors Likely to Express NaPi2b

Clinical Trial IDs

  • ORG STUDY ID: XMT-1536-1
  • NCT ID: NCT03319628

Conditions

  • Platinum Resistant Ovarian Cancer
  • Non Small Cell Lung Cancer Metastatic

Interventions

DrugSynonymsArms
XMT-1536Dose Escalation and Confirmation

Purpose

First-in-human, Phase 1b safety study of the antibody-drug conjugate (ADC) XMT-1536 administered as an intravenous infusion once every four weeks. Patients with tumor types likely to express NaPi2b were enrolled in dose escalation. Patients with platinum-resistant ovarian cancer and non-small cell lung cancer (adenocarcinoma subtype) are being enrolled in the expansion segment of this study. In addition to safety assessments, the pharmacokinetics of the drug will be assessed along with ADC activity.

Detailed Description

      This is a multi-center study of XMT-1536 in patients with tumors likely to express NaPi2b,
      focusing on patients with platinum-resistant ovarian cancer and non-small cell lung cancer,
      adenocarcinoma subtype. XMT-1536 will be administered as an intravenous infusion once every
      four weeks. The study consists of two segments: dose escalation (DES) and expansion (EXP).
      The DES segment studies small groups of patients who receive increased doses. A Safety Review
      Committee has been established to review the data from each dose level before moving to the
      next higher dose. Dose escalation will stop when a patient or patients experience 2 or more
      dose-limiting events. Enrollment into the EXP segment consists of 2 parallel cohorts of
      patients to confirm the dose that has been identified in DES and estimate the objective
      response rate in each patient population. All adverse events will be graded according to the
      National Cancer Institute (NCI) Common Terminology Criteria version (CTCAE v4.03). Throughout
      the study, pharmacokinetics will be measured using proprietary assays developed by Mersana.
      Anti-cancer activity will be measured via RECIST.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation and ConfirmationExperimentalXMT-1536 treatment is administered in groups of patients who will receive doses that increase over time. Once the maximum tolerated dose or recommended Phase 2 dose is achieved, new groups of patients will receive XMT-1536 at this fixed-dose.
  • XMT-1536

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.

        For Ovarian Cancer

          -  Histological diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal
             cancer, excluding the mucinous subtype.

          -  Platinum resistance, defined as disease progression within 6 months of completing a
             platinum-containing chemotherapy regimen.

          -  Not more than 3 prior lines of systemic chemotherapy for ovarian cancer.

          -  Prior use of maintenance therapy is not a line of treatment and is allowed. For NSCLC

          -  Histological diagnosis of nonsquamous NSCLC.

          -  Prior treatment with a platinum-based (cisplatin or carboplatin) regimen and a PD-1 or
             PD-L1 monoclonal antibody (either in combination or sequentially).

          -  Patients with known oncogenic mutations for which there are approved therapies must
             have documented intolerance or disease progression for the approved therapies for
             their mutation.

        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:

               1. Are untreated.

               2. Are progressive.

               3. Or 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.

               4. 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:N/A
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 met
Safety Issue:
Description:Evaluate adverse events and use of concomitant medication use after XMT-1536 doses

Secondary Outcome Measures

Measure:Time of maximum observed concentration of XMT-1536
Time Frame:Daily for one week after first dose; weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
Safety Issue:
Description:Determine the pharmacokinetics of XMT-1536
Measure:Maximum concentration of XMT-1536
Time Frame:Daily for one week after first dose; weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
Safety Issue:
Description:Determine the pharmacokinetics of XMT-1536
Measure:Area under the concentration curve of the last measurable concentration of XMT-1522
Time Frame:Daily for one week after first dose; weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
Safety Issue:
Description:Determine the pharmacokinetics of XMT-1536
Measure:Antineoplastic effects of XMT-1536
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 6 weeks for up to 36 weeks
Safety Issue:
Description:Analyze blood for antibodies to XMT-1536 and neutralizing antibodies

Details

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

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