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First-in-Human Study of XMT-1536 in Cancers 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03319628
Recruitment Status : Recruiting
First Posted : October 24, 2017
Last Update Posted : September 1, 2020
IQVIA Biotech
Information provided by (Responsible Party):
Mersana Therapeutics

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Platinum Resistant Ovarian Cancer Non Small Cell Lung Cancer Metastatic Drug: XMT-1536 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: N/A
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-1536 In Patients With Solid Tumors Likely to Express NaPi2b
Actual Study Start Date : December 12, 2017
Estimated Primary Completion Date : May 30, 2021
Estimated Study Completion Date : December 31, 2021

Arm Intervention/treatment
Experimental: Dose Escalation and Confirmation
XMT-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.
Drug: XMT-1536
XMT-1536 will be administered once every 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.

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 met ]
    Evaluate adverse events and use of concomitant medication use after XMT-1536 doses

Secondary Outcome Measures :
  1. 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 ]
    Determine the pharmacokinetics of XMT-1536

  2. 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 ]
    Determine the pharmacokinetics of XMT-1536

  3. 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 ]
    Determine the pharmacokinetics of XMT-1536

  4. Antineoplastic effects of XMT-1536 [ Time Frame: Every 6 weeks for up to 36 weeks ]
    Monitor tumor size

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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 identifier (NCT number): NCT03319628

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Contact: Donna Jarlenski, MS 617-715-8214

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Sponsors and Collaborators
Mersana Therapeutics
IQVIA Biotech
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Study Director: Dirk Huebner, MD Mersana Therapeutics
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Responsible Party: Mersana Therapeutics Identifier: NCT03319628    
Other Study ID Numbers: XMT-1536-1
First Posted: October 24, 2017    Key Record Dates
Last Update Posted: September 1, 2020
Last Verified: August 2020
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