Platinum-sensitive Ovarian Cancer (UPGRADE-A)Phase 1UPGRADENCT04907968
Study of Upifitamab Rilsodotin in Combination With Carboplatin in Participants With High-grade Serous Ovarian Cancer
A Phase 1 study testing XMT-1536 (Upifitamab Rilsodotin) and Carboplatin in people with Platinum-sensitive Ovarian Cancer (UPGRADE-A), run by Mersana Therapeutics at 1 site in United States.
Trial summary
Phase 1 safety study of the antibody-drug conjugate (ADC) XMT-1536 (upifitamab rilsodotin) administered as an intravenous infusion once every four weeks in combination with Carboplatin in participants with high-grade serous ovarian cancer (HGSOC, including fallopian tube and primary peritoneal cancer). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Platinum-sensitive Ovarian Cancer (UPGRADE-A)
- What is being tested?
- XMT-1536 (Upifitamab Rilsodotin) and Carboplatin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Jun 2021to 3 Oct 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant must be at least 18 years of age, and female; Participant must be able to understand the study procedures and agree to participate in the study by providing informed consent
- Participants must have a histological diagnosis of metastatic or recurrent high-grade serous ovarian cancer, which includes fallopian tube, or primary peritoneal cancer.
- Participant has received 1 to 3 prior lines of therapy for their ovarian cancer; a non-platinum-based chemotherapy regimen is permitted provided it is not the most recent line of therapy. Participant must have platinum-sensitive recurrent disease
- Participant must have an ECOG performance status 0 or 1
- Participant must have measurable 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.
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- 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, or adrenal insufficiency treated with ≤10 mg daily prednisone (or equivalent), after prior taxane therapy are exceptions 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 (WOCBP), or if she is a WOCBP potential and using a contraceptive method that is highly effective.
Who cannot join
- Participant has known sensitivity to any of the study medications, or components thereof, or a history of drug or allergy that contraindicates their participation
- Participant is unable or unlikely to comply with dosing schedule and study evaluations.
- 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 mg x mL/min in the most recent regimen containing carboplatin
- Known history of CTCAE version 5.0 Grade 4 thrombocytopenia OR history of bleeding in association with any grade thrombocytopenia
- 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
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- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Upifitamab Rilsodotin (Xmt-1536) An Open-Label, Multicenter, Dose Escalation And Expansion Study Of Upifitamab Rilsodotin In Combination With Carboplatin In Participants With High Grade Serous Ovarian Cancer (Upgrade-A)
Phase 1 safety study of the antibody-drug conjugate (ADC) XMT-1536 (upifitamab rilsodotin) administered as an intravenous infusion once every four weeks in combination with Carboplatin in participants with high-grade serous ovarian cancer (HGSOC, including fallopian tube and primary peritoneal cancer). The trial consists of dose escalation (DES) and expansion (EXP) portion. In addition to safety assessments, the pharmacokinetics of the drug will be assessed along with ADC activity.
Read the 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 Carboplatinin patients with high-grade serous ovarian cancer (HGSOC, including fallopian tube and primary peritoneal cancer). The trial consists of dose escalation (DES) and expansion (EXP) portion. The primary objective of the dose escalation (DES) portion is to establish the maximum tolerated dose (MTD) for upifitamab rilsodotin in combination with Carboplatin. In the EXP portion of the trial, participants will initiate treatment at the MTD or recommended phase 2 dose (RP2D) determined in the DES for the combination.
- Being tested
- XMT-1536 (Upifitamab Rilsodotin), Carboplatin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XMT-1536 (Upifitamab Rilsodotin)Drug
Also called XMT-1536, UpRi
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.
CarboplatinDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: XMT-1536 (Upifitamab Rilsodotin); Drug: Carboplatin |
| Dose Expansion - Module A (UPGRADE-A) | Experimental | Once the MTD or RP2D is achieved in dose escalation, a new group of patients will receive XMT-1536 (Upifitamab Rilsodotin) at this fixed-dose + carboplatin. Receives: Drug: XMT-1536 (Upifitamab Rilsodotin); Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
DES: Maximum tolerated dose (MTD) for Upifitamab Rilsodotin with carboplatin
Determine the MTD of Upifitamab rilsodotin in combination with carboplatin by evaluating adverse events in combination with carboplatin
Measured: Up to 24 weeks, from the date of first dose until unacceptable side effects or a dose-limiting toxicity is met
EXP: Assess the feasibility of Upifitamab rilsodotin combination initiated at MTD or RP2D
Assess the feasibility of Upifitamab rilsodotin combination initiated at MTD or RP2D Assess the feasibility of Upifitamab rilsodotin combination initiated at MTD or RP2D, 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
Measured: First dose up until 30 days after study termination
Secondary outcomes (12)
DES and EXP: Safety and Tolerability, by observance of frequency and grade of adverse events based on CTCAE v5.0.
DES and EXP: Safety and Tolerability, by observance of frequency and grade of adverse events based on CTCAE v5.0.
Measured: First dose up until 30 days after study termination
DES and EXP: Time of maximum observed concentration of carboplatin
Determine the pharmacokinetics of carboplatin
Measured: Daily for one week after first dose; weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent
DES and EXP: Maximum concentration of XMT-1536 (Upifitamab rilsodotin)
Determine the pharmacokinetics of XMT-1536 (Upifitamab rilsodotin)
Measured: weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
DES and EXP: Maximum concentration of carboplatin
Determine the pharmacokinetics of carboplatin
Measured: Weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
DES and EXP: Area under the concentration curve of the last measurable concentration of XMT-1536 (upifitamab rilsodotin)
Determine the pharmacokinetics of XMT-1536 (Upifitamab rilsodotin)
Measured: Weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
DES and EXP: Area under the concentration curve of the last measurable concentration of carboplatin
Determine the pharmacokinetics of carboplatin
Measured: Weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
DES and EXP: Anti-neoplastic effects of XMT-1536 (Upifitamab rilsodotin) in combination with carboplatin
ORR (by RECIST 1.1)
Measured: Every 8 weeks for the first 12 months, then every 12 weeks on treatment
DES and EXP: Anti-neoplastic effects of XMT-1536 (Upifitamab rilsodotin) in combination with carboplatin
DOR
Measured: Every 8 weeks for the first 12 months, then every 12 weeks on treatment
DES and EXP: Anti-neoplastic effects of XMT-1536 (Upifitamab rilsodotin) in combination with carboplatin
DCR
Measured: Every 8 weeks for the first 12 months, then every 12 weeks on treatment
DES and EXP: Anti-neoplastic effects of XMT-1536 (Upifitamab rilsodotin) in combination with carboplatin PFS (by RECIST 1.1)
PFS (by RECIST 1.1)
Measured: Every 8 weeks for the first 12 months, then every 12 weeks on treatment
DES and EXP: Anti-neoplastic effects of XMT-1536 (Upifitamab rilsodotin) in combination with carboplatin
OS
Measured: Every 90 days
DES and EXP: Assess the correlation of tumor expression of NaPi2b and objective tumor response
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
Measured: Every 8 weeks for the first 12 months, every 12 weeks on treatment, every 90 days for OS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2021
- Study start11 Jun 2021
- Primary completion3 Oct 2023
- Study completion3 Oct 2023
Why it stopped: Study Terminated by Sponsor
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Platinum-sensitive Ovarian Cancer (UPGRADE-A)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mersana Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- IQVIA Biotech, PSI CRO
- Responsible party
- Sponsor
- Investigators
- Brad Sumrow, MD, Study director, Mersana Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04907968
- Sponsor's protocol ID
- XMT-1536-2A
- Acronym
- UPGRADE
- Status last verified
- Oct 2023
- First submitted
- 12 May 2021
- Last updated
- 10 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Upifitamab Rilsodotin (Xmt-1536) An Open-Label, Multicenter, Dose Escalation And Expansion Study Of Upifitamab Rilsodotin In Combination With Carboplatin In Participants With High Grade Serous Ovarian Cancer (Upgrade-A)
- ClinicalTrials.gov ID
- NCT04907968
- Acronym / sponsor ID
- UPGRADE / XMT-1536-2A
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study Terminated by Sponsor
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Mersana TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- IQVIA Biotech, PSI CRO
- Study start
- 11 Jun 2021 (actual)
- Primary completion
- 3 Oct 2023 (actual)
- Study completion
- 3 Oct 2023 (actual)
- First posted
- 1 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 1 safety study of the antibody-drug conjugate (ADC) XMT-1536 (upifitamab rilsodotin) administered as an intravenous infusion once every four weeks in combination with Carboplatin in participants with high-grade serous ovarian cancer (HGSOC, including fallopian tube and primary peritoneal cancer). The trial consists of dose escalation (DES) and expansion (EXP) portion. 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 Carboplatinin patients with high-grade serous ovarian cancer (HGSOC, including fallopian tube and primary peritoneal cancer). The trial consists of dose escalation (DES) and expansion (EXP) portion. The primary objective of the dose escalation (DES) portion is to establish the maximum tolerated dose (MTD) for upifitamab rilsodotin in combination with Carboplatin. In the EXP portion of the trial, participants will initiate treatment at the MTD or recommended phase 2 dose (RP2D) determined in the DES for the combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation - Module A (UPGRADE-A) | Experimental | Drug: XMT-1536 (Upifitamab Rilsodotin), Drug: CarboplatinXMT-1536 (Upifitabmab Rilsodotin) + carboplatin is administered in groups of patients who will receive doses of XMT-1536 that increase over time. |
| Dose Expansion - Module A (UPGRADE-A) | Experimental | Drug: XMT-1536 (Upifitamab Rilsodotin), Drug: CarboplatinOnce the MTD or RP2D is achieved in dose escalation, a new group of patients will receive XMT-1536 (Upifitamab Rilsodotin) at this fixed-dose + carboplatin. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Participant must be at least 18 years of age, and female; Participant must be able to understand the study procedures and agree to participate in the study by providing informed consent
- Participants must have a histological diagnosis of metastatic or recurrent high-grade serous ovarian cancer, which includes fallopian tube, or primary peritoneal cancer.
- Participant has received 1 to 3 prior lines of therapy for their ovarian cancer; a non-platinum-based chemotherapy regimen is permitted provided it is not the most recent line of therapy. Participant must have platinum-sensitive recurrent disease
- Participant must have an ECOG performance status 0 or 1
- Participant must have measurable disease as per RECIST v1.1
Key exclusion criteria (11 listed)
- Participant has known sensitivity to any of the study medications, or components thereof, or a history of drug or allergy that contraindicates their participation
- Participant is unable or unlikely to comply with dosing schedule and study evaluations.
- 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 mg x mL/min in the most recent regimen containing carboplatin
- Known history of CTCAE version 5.0 Grade 4 thrombocytopenia OR history of bleeding in association with any grade thrombocytopenia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XMT-1536 (Upifitamab Rilsodotin)Also: XMT-1536, UpRiDrug: 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. | Drug | Dose Escalation - Module A (UPGRADE-A), Dose Expansion - Module A (UPGRADE-A) |
| CarboplatinDrug: 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. | Drug | Dose Escalation - Module A (UPGRADE-A), Dose Expansion - Module A (UPGRADE-A) |
Primary outcome
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
EXP: Assess the feasibility of Upifitamab rilsodotin combination initiated at MTD or RP2D
Time frame: First dose up until 30 days after study termination
Assess the feasibility of Upifitamab rilsodotin combination initiated at MTD or RP2D Assess the feasibility of Upifitamab rilsodotin combination initiated at MTD or RP2D, 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
12 secondary outcomes
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
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
DES and EXP: Maximum concentration of XMT-1536 (Upifitamab rilsodotin)
Time frame: weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
DES and EXP: Maximum concentration of carboplatin
Time frame: Weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
DES and EXP: Area under the concentration curve of the last measurable concentration of XMT-1536 (upifitamab rilsodotin)
Time frame: Weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
DES and EXP: Area under the concentration curve of the last measurable concentration of carboplatin
Time frame: Weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses
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
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
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
DES and EXP: Anti-neoplastic effects of XMT-1536 (Upifitamab rilsodotin) in combination with carboplatin PFS (by RECIST 1.1)
Time frame: Every 8 weeks for the first 12 months, then every 12 weeks on treatment
DES and EXP: Anti-neoplastic effects of XMT-1536 (Upifitamab rilsodotin) in combination with carboplatin
Time frame: Every 90 days
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
Results and safety
The study was stopped early (reason given: Study Terminated by Sponsor). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2023.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brad Sumrow, MD study director
Mersana Therapeutics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing XMT-1536 (Upifitamab Rilsodotin) and Carboplatin in people with Platinum-sensitive Ovarian Cancer (UPGRADE-A), run by Mersana Therapeutics at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study Terminated by Sponsor). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2023.