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Study of Upifitamab Rilsodotin in Combination With Other Agent(s) in Participants With High-grade Serous Ovarian Cancer (UPGRADE)

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ClinicalTrials.gov Identifier: NCT04907968
Recruitment Status : Recruiting
First Posted : June 1, 2021
Last Update Posted : September 16, 2021
Sponsor:
Collaborator:
IQVIA Biotech
Information provided by (Responsible Party):
Mersana Therapeutics

Brief Summary:
Phase 1/2 safety study of the antibody-drug conjugate (ADC) XMT-1536 (upifitamab rilsodotin) administered as an intravenous infusion once every four weeks in combination with other agent(s) in participants with high-grade serous ovarian cancer (HGSOC, including fallopian tube and primary peritoneal cancer). This study has an umbrella design. The trial consists of dose escalation (DES) and expansion (EXP) portions for specific combinations outlined in various modules. In addition to safety assessments, the pharmacokinetics of the drug will be assessed along with ADC activity.

Condition or disease Intervention/treatment Phase
Platinum-sensitive Ovarian Cancer (UPGRADE-A) Drug: XMT-1536 (Upifitamab Rilsodotin) Drug: Carboplatin Phase 1 Phase 2

Detailed Description:
This trial is an open-label, multi-center Phase 1 study of upifitamab rilsodotin administered as an intravenous infusion once every 28 days in combination with platinum-containing agents in patients with high-grade serous ovarian cancer (HGSOC, including fallopian tube and primary peritoneal cancer). This study has an umbrella design. The trial consists of dose escalation (DES) and expansion (EXP) portions. The primary objective of the dose escalation (DES) portion is to establish the maximum tolerated dose (MTD) for upifitamab rilsodotin in combination with other agent(s). In the EXP portion of the trial, participants will initiate treatment at the MTD determined in the DES for the combination. The other agent(s) in this first combination-specific module, Module A (UPGRADE-A) is carboplatin.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Multicenter, Dose Escalation and Expansion Modular, Umbrella Master Study of Upifitamab Rilsodotin in Combination With Other Agent(s) In Participants With High-grade Serous Ovarian Cancer (UPGRADE)
Actual Study Start Date : June 11, 2021
Estimated Primary Completion Date : November 2023
Estimated Study Completion Date : July 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ovarian Cancer
Drug Information available for: Carboplatin

Arm Intervention/treatment
Experimental: Dose Escalation - Module A (UPGRADE-A)
XMT-1536 (Upifitabmab Rilsodotin) + carboplatin is administered in groups of patients who will receive doses of XMT-1536 that increase over time.
Drug: XMT-1536 (Upifitamab Rilsodotin)
XMT-1536 (Upifitamab Rilsodotin) will be administered on Day 1 of each 28 day cycle 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
Other Names:
  • XMT-1536
  • UpRi

Drug: Carboplatin
Carboplatin will be administered on Day 1 on each of the first six 28 day cycles.

Experimental: Dose Expansion - Module A (UPGRADE-A)
Once the maximum tolerated dose or recommended Phase 2 dose is achieved in dose escalation, a new group of patients will receive XMT-1536 (Upifitamab Rilsodotin) at this fixed-dose + carboplatin.
Drug: XMT-1536 (Upifitamab Rilsodotin)
XMT-1536 (Upifitamab Rilsodotin) will be administered on Day 1 of each 28 day cycle 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
Other Names:
  • XMT-1536
  • UpRi

Drug: Carboplatin
Carboplatin will be administered on Day 1 on each of the first six 28 day cycles.




Primary Outcome Measures :
  1. DES: Maximum tolerated dose (MTD) for Upifitamab Rilsodotin with carboplatin [ Time Frame: Up to 24 weeks, from the date of first dose until unacceptable side effects or a dose-limiting toxicity is met ]
    Determine the MTD of upifitamab rilsodotin in combination with carboplatin by evaluating adverse events in combination with carboplatin

  2. EXP: Assess the feasibility of upifitamab rilsodotin combination initiated at MTD [ Time Frame: First dose up until 30 days after study termination ]
    Assess the feasibility of upifitamab rilsodotin combination initiated at MTD, where the regimen will be considered feasible if at least 60% of participants complete at least four cycles of the carboplatin-upifitamab rilsodotin combination, allowing for standard treatment modifications, without discontinuing treatment earlier for reasons other than disease progression


Secondary Outcome Measures :
  1. DES and EXP: Safety and Tolerability, by observance of frequency and grade of adverse events based on CTCAE v5.0. [ Time Frame: First dose up until 30 days after study termination ]
  2. DES and EXP: Time of maximum observed concentration of carboplatin [ 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 ]
    Determine the pharmacokinetics of carboplatin

  3. DES and EXP: Maximum concentration of XMT-1536 (upifitamab rilsodotin) [ 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 (upifitamab rilsodotin)

  4. DES and EXP: Maximum concentration of carboplatin [ 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 carboplatin

  5. DES and EXP: Area under the concentration curve of the last measurable concentration of XMT-1536 (upifitamab rilsodotin) [ 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 (upifitamab rilsodotin)

  6. DES and EXP: Area under the concentration curve of the last measurable concentration of carboplatin [ 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 carboplatin

  7. DES and EXP: Anti-neoplastic effects of XMT-1536 (upifitamab rilsodotin) in combination with carboplatin [ Time Frame: Every 8 weeks for the first 12 months, then every 12 weeks on treatment ]
    ORR (by RECIST 1.1)

  8. DES and EXP: Anti-neoplastic effects of XMT-1536 (upifitamab rilsodotin) in combination with carboplatin [ Time Frame: Every 8 weeks for the first 12 months, then every 12 weeks on treatment ]
    DOR

  9. DES and EXP: Anti-neoplastic effects of XMT-1536 (upifitamab rilsodotin) in combination with carboplatin [ Time Frame: Every 8 weeks for the first 12 months, then every 12 weeks on treatment ]
    DCR

  10. DES and EXP: Anti-neoplastic effects of XMT-1536 (upifitamab rilsodotin) in combination with carboplatin [ Time Frame: Every 8 weeks for the first 12 months, then every 12 weeks on treatment ]
    PFS (by RECIST 1.1)

  11. DES and EXP: Anti-neoplastic effects of XMT-1536 (upifitamab rilsodotin) in combination with carboplatin [ Time Frame: Every 90 days ]
    OS

  12. DES and EXP: Assess the correlation of tumor expression of NaPi2b and objective tumor response [ Time Frame: Every 8 weeks for the first 12 months, every 12 weeks on treatment, every 90 days for OS ]
    Potential NaPi2b protein or RNA levels of NaPi2b transcript or other genes related to cancer measured in tumor samples Blood-based biomarkers, which may include serum cytokines, circulating immune cells, and circulating tumor cells



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:   Female
Accepts Healthy Volunteers:   No
Criteria

General Inclusion Criteria:

  • Participants must have a histological diagnosis of metastatic or recurrent high-grade serous ovarian cancer, which includes fallopian tube, or primary peritoneal cancer.

General Exclusion Criteria:

  • Participant is unable or unlikely to comply with dosing schedule and study evaluations.

UPGRADE-A Combination-specific Inclusion Criteria:

  • Participant has received 1 to 2 prior lines of platinum-containing chemotherapy for their ovarian cancer. They must have platinum-sensitive recurrent disease
  • Participant must have an ECOG performance status 0 or 1
  • Participant must have measurable or evaluable disease as per RECIST v1.1
  • Tumor sample must be provided, either an archival tumor tissue block or slides or, if not available, a tumor tissue block or slides from a new tumor biopsy obtained through a low-risk, medically routine procedure.
  • Participants with toxicity from prior therapy or surgical procedures must have recovered to ≤ Grade 1. Participants with alopecia, stable immune-related toxicity such as hypothyroidism on hormone replacement, adrenal insufficiency treated with ≤10 mg daily prednisone (or equivalent), or chronic Grade 2 peripheral sensory neuropathy after prior taxane therapy is an exception to this criterion and may qualify for this study.
  • Participants must have cardiac left ventricular ejection fraction (LVEF) ≥50% or ≥ the institution's lower limit of normal as measured by either Echo or MUGA scan
  • Participants must have adequate organ function within 14 days prior to enrollment
  • A female participant is eligible to participate if she is not pregnant or breastfeeding, if she is not a woman of childbearing potential, or if she is a woman of childbearing potential and using a contraceptive method that is highly effective.

UPGRADE-A Combination-specific Exclusion Criteria:

  • Participant has a prior hypersensitivity reaction to carboplatin requiring desensitization or discontinuation.
  • Participant has prior platelet or neutrophil toxicity to carboplatin-containing therapy requiring dose reduction to AUC <5.
  • Participant has had major surgery within 28 days of starting study treatment, systemic anticancer therapy within the lesser of 28 days or 5 half-lives of the prior therapy before starting study treatment (14 days or 5 half-lives for small molecule targeted therapy), or recent radiation therapy with unresolved toxicity or within a time window of potential toxicity
  • Participant has received prior treatment with mirvetuximab soravtansine or another ADC containing an auristatin or maytansinoid payload.
  • Participant has untreated CNS metastases (including new and progressive brain metastases), history of leptomeningeal metastasis, or carcinomatous meningitis.
  • Has a diagnosis of additional malignancy that required treatment within 2 years prior to screening, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix
  • Participant is unwilling to be transfused with blood components.
  • Participant is receiving concurrent anti-cancer therapy (e.g. chemotherapy, radiation therapy, biologic therapy, immunotherapy, hormonal therapy, investigational therapy).

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): NCT04907968


Contacts
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Contact: Cassandra Carrington 617-498-0020 ccarrington@mersana.com

Locations
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United States, Massachusetts
Lahey Clinic Recruiting
Burlington, Massachusetts, United States, 01805
Contact: Amanda Cossar    781-744-3071    Amanda.cossar@lahey.org   
Principal Investigator: Corrine Zarwan         
United States, Michigan
START Midwest Recruiting
Grand Rapids, Michigan, United States, 49546
Contact: Kathy Estkowski    616-954-5551    Kathy.estkowski@startmidwest.com   
Principal Investigator: Nehal Lakhani, MD         
United States, South Carolina
Greenville Hospital System University Medical Center Recruiting
Greenville, South Carolina, United States, 29605
Contact: Patty Phillips       patty.phillips@prismahealth.org   
Contact: Gerry Hendricks       gerry.hendricks@prismahealth.org   
Principal Investigator: Jeffery Edenfield, MD         
Sponsors and Collaborators
Mersana Therapeutics
IQVIA Biotech
Investigators
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Study Director: Robert Burger, MD Mersana Therapeutics
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Responsible Party: Mersana Therapeutics
ClinicalTrials.gov Identifier: NCT04907968    
Other Study ID Numbers: XMT-1536-2
First Posted: June 1, 2021    Key Record Dates
Last Update Posted: September 16, 2021
Last Verified: August 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carboplatin
Antineoplastic Agents