A Three-Part Phase 3 Study of Sofetabart Mipitecan in Participants With Platinum-Resistant (Part A) and Platinum-Sensitive (Parts B and C) Ovarian Cancer

Phase 3RecruitingNCT07213804

Eli Lilly and Company1,630 enrolled

Overview

This is a clinical study that has three parts. It is testing a potential new medicine called Sofetabart Mipitecan (Sofe-M) for people with certain types of ovarian, peritoneal, and fallopian tube cancers. Part A enrolls participants with platinum-resistant cancer, meaning their disease progressed during or within six months of platinum-based chemotherapy. Parts B and C enroll participants with platinum-sensitive cancer, whose disease responded and remained controlled for at least six months after completing platinum treatment. The researchers want to find out if Sofe-M works better than the standard treatments that doctors use now and to better understand how safe it is. Each participant's time in the study will depend on how they respond to the treatment.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

1,630

Conditions

Ovarian Neoplasms Fallopian Tube Neoplasms Peritoneal Neoplasms Neoplasm Metastasis

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: Part A, B, and C: * Have histologically confirmed high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer. * Have confirmed availability of tumor tissue block or slides * Have radiographic progression on or after most recent line of systemic anticancer therapy * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. * Have measurable disease per RECIST v1.1 Part A: * Have platinum-resistant disease, defined as radiographic progression less than or equal to (≤)6 months of the last administration of platinum therapy. * Have previously received 1 to 3 prior lines of systemic cytotoxic therapy. Up to 4 lines of prior cytotoxic therapy is allowed if one of those lines is mirvetuximab soravtansine. * Have received prior bevacizumab treatment, unless documented contraindication or intolerance. * Have received treatment with a poly (ADP-ribose) polymerase inhibitor (PARPi) if known to have a somatic or germline breast cancer gene (BRCA) mutation, if clinically indicated, unless documented contraindication or intolerance. Part B and C: * Have relapsed after first-line platinum-based chemotherapy and have platinum-sensitive disease defined as radiographic progression greater than (\>)6 months of their last administration of platinum therapy * Have previously received 1 to 2 prior lines of systemic cytotoxic chemotherapy Part B: \- Have previously received a PARPi, per local product label, with progression on, or within 6 months of completion of PARPi treatment. Part C: \- Have not previously received a PARPi treatment. Exclusion Criteria: Parts A, B and C: \- Have received prior antibody-drug conjugate (ADC) with a topoisomerase inhibitor payload. Part A: * Have primary platinum-refractory disease, defined as radiographic progression ≤ 1 month since the last dose of first-line platinum-containing chemotherapy. Part B and C: \- Have clinically significant proteinuria Part C: \- Have a known pathogenic BRCA1/2 gene alteration (somatic or germline).

Outcomes

Primary Outcomes

Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Investigator

PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Investigator

Time frame: Randomization to radiographic progression or death from any cause (up to 70 months)

PFS per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Blinded, Independent, Central Review (BICR)

Time frame: Randomization to radiographic progression or death from any cause (up to 70 months)

Secondary Outcomes

Overall Survival (OS)

Time frame: Randomization to date of death from any cause (up to 70 months)

PFS

PFS by blinded independent central review (BICR)

Time frame: Randomization to radiographic progression or death from any cause (up to 70 months)

Overall Response Rate (ORR): Proportion of Participants who Achieve a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR)

ORR per RECIST v1.1

Time frame: Randomization to disease progression or death (up to 70 months)

Duration of Response (DOR)

DOR per RECIST v1.1

Time frame: Date of first documented CR or PR to date of radiographic progression or death from any cause (up to 70 months)

Disease Control Rate (DCR): Proportion of Participants who Achieve a BOR of CR, PR, or Stable Disease (SD)

DCR per RECIST v1.1

Time frame: Randomization to disease progression or death from any cause (up to 70 months)

PFS2

Time frame: Randomization to disease progression on next line of treatment or death from any cause (up to 70 months)

Time to Initiation of First Subsequent Systemic Anticancer Therapy or Death (TNTD)

Time frame: Randomization to initiation of subsequent systemic anticancer or death from any cause (up to 70 months)

Proportion of Participants with Response of Cancer Antigen-125 (CA-125) per Gynecologic Cancer Intergroup Criteria (GCIG)

Per GCIG

Time frame: Randomization to 30 days post treatment discontinuation

Percentage of Assessments with High Side-effect Bother, as measured by Functional Assessment of Cancer Therapy - General Item 5 (FACT GP5)

FACT-GP5 is a single-item, patient-reported instrument for assessing overall treatment side-effect burden. High side effect bother is defined as a score of 3 or 4 on a 5-point Likert scale. Higher scores represent higher symptom burden.

Time frame: Randomization to 30 days post treatment discontinuation

Change from Baseline in Abdominal/GI Symptoms, as measured by the European Organization for Research and Treatment of Cancer Ovarian Cancer Module (EORTC OV28)

The EORTC OV28 consists of 28 items covering 3 functional scales and 5 symptom scales. The Abdominal/GI symptom scale ranges from 0 to 100. Higher scores indicate worse symptoms.

Time frame: Randomization to 30 days post treatment discontinuation

Change from Baseline in Overall Health-related Quality of Life (HRQoL), as measured by the EORTC QLQ-C30 Global Health Status/Quality of Life Subscale

The EORTC QLQ-C30 is a 30-question patient-reported instrument used to assess multidimensional HRQoL in cancer patients. Overall HRQoL is measured by the EORTC QLQ-30 Global Health Status/Quality of Life Subscale (two items). Response options range from 0 - 100. Higher score represents better overall HRQoL.

Time frame: Randomization to 30 days post treatment discontinuation

Pharmacokinetics (PK): Minimum Blood Plasma Concentration (Cmin) of LY4170156

Time frame: Randomization through end of treatment (up to 70 months)]

PFS

PFS by investigator assessment per RECIST v1.1

Time frame: Randomization to radiographic progression or death from any cause (up to 70 months)

A Three-Part Phase 3 Study of Sofetabart Mipitecan in Participants With Platinum-Resistant (Part A) and Platinum-Sensitive (Parts B and C) Ovarian Cancer

Overview

Conditions

Interventions

Eligibility

Locations (267)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts