Clinical Trials /

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

NCT04907968

Description:

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.

Related Conditions:
  • High Grade Fallopian Tube Serous Adenocarcinoma
  • High Grade Ovarian Serous Adenocarcinoma
  • Primary Peritoneal Serous Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of Upifitamab Rilsodotin in Combination With Other Agent(s) in Participants With High-grade Serous Ovarian Cancer
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: XMT-1536-2
  • NCT ID: NCT04907968

Conditions

  • Platinum-sensitive Ovarian Cancer (UPGRADE-A)

Interventions

DrugSynonymsArms
XMT-1536 (Upifitamab Rilsodotin)XMT-1536, UpRiDose Escalation - Module A (UPGRADE-A)
CarboplatinDose Escalation - Module A (UPGRADE-A)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation - Module A (UPGRADE-A)ExperimentalXMT-1536 (Upifitabmab Rilsodotin) + carboplatin is administered in groups of patients who will receive doses of XMT-1536 that increase over time.
  • XMT-1536 (Upifitamab Rilsodotin)
  • Carboplatin
Dose Expansion - Module A (UPGRADE-A)ExperimentalOnce 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.
  • XMT-1536 (Upifitamab Rilsodotin)
  • Carboplatin

Eligibility 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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Determine the MTD of upifitamab rilsodotin in combination with carboplatin by evaluating adverse events in combination with carboplatin

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:Determine the pharmacokinetics of carboplatin
Measure: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
Safety Issue:
Description:Determine the pharmacokinetics of XMT-1536 (upifitamab rilsodotin)
Measure: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
Safety Issue:
Description:Determine the pharmacokinetics of carboplatin
Measure: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
Safety Issue:
Description:Determine the pharmacokinetics of XMT-1536 (upifitamab rilsodotin)
Measure: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
Safety Issue:
Description:Determine the pharmacokinetics of carboplatin
Measure: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
Safety Issue:
Description:ORR (by RECIST 1.1)
Measure: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
Safety Issue:
Description:DOR
Measure: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
Safety Issue:
Description:DCR
Measure: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
Safety Issue:
Description:PFS (by RECIST 1.1)
Measure:DES and EXP: Anti-neoplastic effects of XMT-1536 (upifitamab rilsodotin) in combination with carboplatin
Time Frame:Every 90 days
Safety Issue:
Description:OS
Measure: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
Safety Issue:
Description: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

Details

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

Last Updated

June 28, 2021