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.
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
Drug | Synonyms | Arms |
---|
XMT-1536 (Upifitamab Rilsodotin) | XMT-1536, UpRi | Dose Escalation - Module A (UPGRADE-A) |
Carboplatin | | Dose 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
Name | Type | Description | Interventions |
---|
Dose Escalation - Module A (UPGRADE-A) | Experimental | XMT-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) | Experimental | 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. | - 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
August 13, 2021