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

NCT04907968 | Terminated Phase 1 FDA Drug

• 1 other identifier: XMT-1536-2A
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Platinum-sensitive Ovarian Cancer (UPGRADE-A)

Outcome Measures

Primary Outcomes (2)

• 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

  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

  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.

  First dose up until 30 days after study termination

• DES and EXP: Time of maximum observed concentration of carboplatin

  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)

  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

  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)

  Weekly until 28 days after first dose; immediately before and after and 1 week after all subsequent doses

Study Arms (2)

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.

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.

Drug: XMT-1536 (Upifitamab Rilsodotin); Drug: Carboplatin

Interventions

XMT-1536 (Upifitamab Rilsodotin) 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.

Also known as: XMT-1536, UpRi

Dose Escalation - Module A (UPGRADE-A); Dose Expansion - Module A (UPGRADE-A)

Carboplatin 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 Escalation - Module A (UPGRADE-A); Dose Expansion - Module A (UPGRADE-A)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Mersana Therapeutics: lead
• IQVIA Biotech: collaborator
• PSI CRO: collaborator

Study Sites (1)

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

MeSH Terms

Interventions

Carboplatin

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Brad Sumrow, MD

  Mersana Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2021
• First Posted: June 1, 2021
• Study Start: June 11, 2021
• Primary Completion: October 3, 2023
• Study Completion: October 3, 2023
• Last Updated: October 10, 2023

Record last verified: 2023-10

Locations

US (1)