A Study of LY4170156 in Participants With Selected Advanced Solid Tumors

NCT06400472RecruitingPHASE1INTERVENTIONAL

Summary

The purpose of this study is to find out whether the study drug, LY4170156, is safe, tolerable and effective in participants with advanced solid tumors. The study is conducted in two parts - phase Ia (dose-escalation, dose-optimization) and phase Ib (dose-expansion). The study will last up to approximately 4 years.

Key Facts

Lead Sponsor

Eli Lilly and Company

Enrollment

495

Start Date

2024-05-20

Completion Date

2027-02-01

Study Type

INTERVENTIONAL

Official Title

A First-in-Human, Phase 1a/1b Trial to Assess the Safety, Tolerability and Preliminary Efficacy of LY4170156, an Antibody-Drug Conjugate Targeting Folate Receptor α-Expressing Tumor Cells, in Participants With Selected Advanced Solid Tumors

Interventions

LY4170156bevacizumabcarboplatinItraconazolepembrolizumab

Conditions

Ovarian NeoplasmsEndometrial NeoplasmsUterine Cervical NeoplasmsCarcinomaNon-Small-Cell LungTriple Negative Breast NeoplasmsPancreatic NeoplasmColorectal Neoplasms

Eligibility

Age Range

18 Years+

Sex

ALL

Inclusion Criteria:

* Have one of the following solid tumor cancers:

  * Dose Escalation: Ovarian (epithelial ovarian, primary peritoneal, and fallopian tube) cancer, endometrial cancer, cervical cancer, non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), pancreatic cancer, or colorectal cancer (CRC)
  * Dose Optimization: Ovarian (epithelial ovarian, primary peritoneal, and fallopian tube) and endometrial cancer
  * Dose Expansion: Low grade serous ovarian cancer, cervical cancer, NSCLC, and TNBC

Exclusion Criteria:

* Individual with known or suspected uncontrolled central nervous system (CNS) metastases
* Individual with history of carcinomatous meningitis
* Individual with active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
* Individual with evidence of corneal keratopathy or history of corneal transplant
* Any serious unresolved toxicities from prior therapy
* Significant cardiovascular disease
* Prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 milliseconds (ms)
* History of pneumonitis/interstitial lung disease
* Individuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention

Outcome Measures

Primary Outcomes

Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY4170156

Number of participants with dose-limiting toxicities (DLTs)

Time frame: 1 Cycle (21 days)

Phase 1a: To determine the RP2D or optimal dose of LY4170156 with bevacizumab

Number of participants with DLTs

Time frame: 1 Cycle (21 days)

Phase 1a: To determine the RP2D or optimal dose of LY4170156 with carboplatin

Number of participants with DLTs

Time frame: 1 Cycle (21 days)

Phase 1a: To determine the RP2D or optimal dose of LY4170156 with pembrolizumab

Number of participants with DLTs

Time frame: 1 Cycle (21 days)

Phase 1b: To assess the antitumor activity of LY4170156 Monotherapy: Overall response rate (ORR)

ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)

Time frame: Up to Approximately 48 Months or 4 Years

Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration

A summary of SAEs regardless of causality, will be reported in the Reported Adverse Events module

Time frame: Up to Approximately 48 Months or 4 Years

Secondary Outcomes

To characterize the pharmacokinetics (PK) properties of LY4170156: Minimum Plasma Concentration (Cmin)

PK: Cmin of LY4170156

Time frame: First 4 Cycles (84 days)

To characterize the PK properties of LY4170156: Cmin with bevacizumab or carboplatin

PK: Cmin of LY4170156

Time frame: First 4 Cycles (Approximately 84 days)

To characterize the PK properties of LY4170156: Cmin with pembrolizumab

PK: Cmin of LY4170156

Time frame: First 4 Cycles (84 days)

To characterize the PK properties of LY4170156: Area under the concentration versus time curve (AUC)

PK: AUC of LY4170156

Time frame: First 4 Cycles (84 days)

To evaluate the preliminary antitumor activity of LY4170156: Overall response rate (ORR)

ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)

Time frame: Up to Approximately 48 Months or 4 Years

To evaluate the preliminary antitumor activity of LY4170156: Overall response rate (ORR) with bevacizumab or carboplatin or pembrolizumab

ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)

Time frame: Up to Approximately 48 Months or 4 Years

To evaluate the preliminary antitumor activity of LY4170156: Duration of response (DOR)

DOR per investigator assessed RECIST 1.1

Time frame: Up to Approximately 48 Months or 4 Years

To evaluate the preliminary antitumor activity of LY4170156: Duration of response (DOR) with bevacizumab or carboplatin or pembrolizumab

DOR per investigator assessed RECIST 1.1

Time frame: Up to Approximately 48 Months or 4 Years

To evaluate the preliminary antitumor activity of LY4170156: Time to response (TTR)

TTR per investigator assessed RECIST 1.1

Time frame: Up to Approximately 48 Months or 4 Years

To evaluate the preliminary antitumor activity of LY4170156: Time to response (TTR) with bevacizumab or carboplatin or pembrolizumab

TTR per investigator assessed RECIST 1.1

Time frame: Up to Approximately 48 Months or 4 Years

To evaluate the preliminary antitumor activity of LY4170156: Progression free survival (PFS)

PFS per investigator assessed RECIST 1.1

Time frame: Up to Approximately 48 Months or 4 Years

To evaluate the preliminary antitumor activity of LY4170156: Progression free survival (PFS) with bevacizumab or carboplatin or pembrolizumab

PFS per investigator assessed RECIST 1.1

Time frame: Up to Approximately 48 Months or 4 Years]

To evaluate the preliminary antitumor activity of LY4170156: Disease control rate (DCR)

DCR per investigator assessed RECIST 1.1

Time frame: Up to Approximately 48 Months or 4 Years

To evaluate the preliminary antitumor activity of LY4170156: Disease control rate (DCR) with bevacizumab or carboplatin or pembrolizumab

DCR per investigator assessed RECIST 1.1

Time frame: Up to Approximately 48 Months or 4 Years

Locations

HonorHealth, Scottsdale, United States

University of California, San Diego (UCSD) - Moores Cancer Center, La Jolla, United States

South Texas Accelerated Research Therapeutics (START) Midwest, Grand Rapids, United States

NYU Langone Health - Long Island, Mineola, United States

New York University (NYU) Clinical Cancer Center, New York, United States

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center, New York, United States

The Ohio State University (OSU) Wexner Medical Center, Columbus, United States

The University of Texas - MD Anderson Cancer Center, Houston, United States

START Mountain Region, West Valley City, United States

Cancer Research SA, Adelaide, Australia

Icon Cancer Centre South Brisbane, QLD, Australia

Centre Leon Berard, Lyon, France

Institut de Cancerologie de l'Ouest - site St-Herblain, Saint-Herblain, France

Oncopole Claudius Regaud, Toulouse, France

Istituto Europeo di Oncologia, Milan, Italy

Istituto Clinico Humanitas, Rozzano, Italy

Shizuoka Cancer Center, Shizuoka, Japan

National Cancer Center Hospital, Tokyo, Japan

Cancer Institute Hospital of JFCR, Tokyo, Japan

National Cancer Center, Goyang-si Gyeonggi-do, South Korea

Hospital Universitario Vall d'Hebron, Barcelona, Spain

Hospital Universitario 12 de Octubre, Madrid, Spain

Hospital Clinico Universitario de Valencia, Valencia, Spain

Linked Diseases

Ovarian Neoplasms

Ovarian Neoplasms — a type of gynecological cancer.

Endometrial Neoplasms

Endometrial Neoplasms — a type of gynecological cancer.

Uterine Cervical Neoplasms

Uterine Cervical Neoplasms — a type of gynecological cancer.