Study of Upifitamab Rilsodotin in Combination With Carboplatin in Participants With High-grade Serous Ovarian Cancer

NCT ID: NCT04907968

Last Updated: 2023-10-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-11
• Study Completion Date: 2023-10-03

Brief 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). 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.

Conditions

Platinum-sensitive Ovarian Cancer (UPGRADE-A)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

XMT-1536 (Upifitamab Rilsodotin)

Intervention Type: DRUG

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.

Carboplatin

Intervention Type: DRUG

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.

Dose Expansion - Module A (UPGRADE-A)

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.

Group Type: EXPERIMENTAL

XMT-1536 (Upifitamab Rilsodotin)

Intervention Type: DRUG

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.

Carboplatin

Intervention Type: DRUG

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.

Interventions

XMT-1536 (Upifitamab Rilsodotin)

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

XMT-1536; UpRi

Eligibility Criteria

Inclusion Criteria

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.
• 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.

Exclusion Criteria

• 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
• 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

IQVIA Biotech

INDUSTRY

Sponsor Role: collaborator

PSI CRO

INDUSTRY

Sponsor Role: collaborator

Mersana Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brad Sumrow, MD

Role: STUDY_DIRECTOR

Mersana Therapeutics

Locations

START Midwest

Grand Rapids, Michigan, United States

Countries

United States

Other Identifiers

XMT-1536-2A

Identifier Type: -

Identifier Source: org_study_id