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

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ClinicalTrials.gov Identifier: NCT03319628
Recruitment Status : Recruiting
First Posted : October 24, 2017
Last Update Posted : September 17, 2018
Sponsor:
Collaborator:
Novella Clinical
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 three weeks. Patients with tumor types likely to express NaPi2b will be enrolled. 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 Papillary Renal Cell Carcinoma Papillary Thyroid Cancer Salivary Gland Cancer 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-squamous non-small cell lung cancer. XMT-1536 will be administered as an intravenous infusion once every three weeks. The study consists of two segments: dose escalation (DES) and expansion (EXP). The DES segment will study small groups of patients who receive increased doses. A Safety Review Committee will be 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. At this point, the maximum tolerated dose or recommended Phase 2 dose will be established and the EXP segment will begin. This segment consists of 3 parallel cohorts of patients to confirm the MTD or RP2D and estimate the objective response rate in each selected 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. ADC activity will be measured via RECIST.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Open-label, dose escalation to reach MTD. The MTD will be confirmed in 3 parallel cohorts: (1) patients with platinum-resistant ovarian cancer; (2) patients with non-squamous NSCLC; and (3) patients with papillary thyroid carcinoma, endometrial carcinoma, papillary renal cell carcinoma, or salivary duct carcinoma.
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 : June 1, 2019
Estimated Study Completion Date : January 30, 2020


Arm Intervention/treatment
Experimental: Dose Escalation and Confirmation
XMT-1536 treatment will be 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-1535 will be administered once every 21 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 14 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 21 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 21 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 21 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 up to 12 months ]
    Monitor tumor size

  5. Anti-drug antibody and neutralizing antibody [ Time Frame: Every 6 weeks up to 12 month ]
    Analyze blood for antibodies to XMT-1536 and neutralizing antibodies



Information from the National Library of Medicine

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

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.

For Other Indications

  • For papillary thyroid carcinoma patients:

    1. Progressive, radioactive iodine-refractory, loco-regional recurrent or metastatic disease.
    2. Resistance or intolerance to prior kinase inhibitor therapy (e.g., lenvatinib, sorafenib). A patient who is considered inappropriate for, or who has refused, kinase inhibitor therapy may be enrolled with approval of the Medical Monitor.
  • For endometrial carcinoma patients, a diagnosis of epithelial endometrial carcinoma is required. Stromal tumors and carcinosarcoma (mixed malignant Mullerian tumor) are excluded.
  • For papillary renal cell carcinoma patients, the following are required:

    1. Documented local confirmation of renal cell carcinoma with a predominantly papillary growth pattern.
    2. Progression after standard systemic therapy or a lack of available effective therapy, in the assessment of the Investigator.
  • For salivary duct carcinoma patients, the following are required:

    1. A histologic diagnosis of salivary duct carcinoma (other subtypes of salivary gland cancer are excluded).
    2. Progression after standard systemic therapy or a lack of available effective therapy, in the assessment of the Investigator.

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.

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 ClinicalTrials.gov identifier (NCT number): NCT03319628


Contacts
Contact: Donna Jarlenski, MS 617-715-8214 djarlenski@mersana.com

Locations
United States, Massachusetts
Dana Farber Cancer Insititute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Nadia Kianfar         
United States, Oklahoma
Stephenson Cancer Centre-University of Oklahoma Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Natshia Moreno, RN         
United States, Pennsylvania
University of Pittsburgh Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15218
Contact: linda Armstrong, RN         
United States, South Carolina
Institute of Transnational Oncology-Greenville Hospital System University Medical Center Recruiting
Greenville, South Carolina, United States, 29604
Contact: Jan Kueber         
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: http://sarahcannon.com/searchct/results.dot         
United States, Texas
South Texas Accelerated Research Therapeutics (START) Recruiting
San Antonio, Texas, United States, 78229
Contact: Isabel Jimenez, RN, MSN    210-593-5252    isabel.jimenez@startsa.com   
Principal Investigator: Anthony W. Tolcher, MD, FRCP         
NEXT Oncology Recruiting
San Antonio, Texas, United States, 78240
Sponsors and Collaborators
Mersana Therapeutics
Novella Clinical
Investigators
Study Director: Eric Hailman, MD, PhD Mersana Therapeutics

Responsible Party: Mersana Therapeutics
ClinicalTrials.gov Identifier: NCT03319628     History of Changes
Other Study ID Numbers: XMT-1536-1
First Posted: October 24, 2017    Key Record Dates
Last Update Posted: September 17, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Renal Cell
Thyroid Neoplasms
Salivary Gland Neoplasms
Carcinoma
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Endocrine Gland Neoplasms
Head and Neck Neoplasms
Endocrine System Diseases
Thyroid Diseases
Mouth Neoplasms
Mouth Diseases
Stomatognathic Diseases
Salivary Gland Diseases