Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Breast Neoplasms

Adenocarcinoma

Triple Negative Breast Neoplasms

Carcinoma, Squamous Cell

Sarcoma

Carcinoma, Hepatocellular

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Histiocytoma, Malignant Fibrous

Leiomyosarcoma

Squamous Cell Carcinoma of Head and Neck

Histiocytoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Connective and Soft Tissue

Breast Diseases

Skin Diseases

Head and Neck Neoplasms

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Ovarian Cancer

Ovarian Epithelial Cancer

Soft Tissue Sarcoma

Undifferentiated Pleomorphic Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants received intravenous (IV) push or IV bolus infusion of 10 mg LY3435151.

Pembrolizumab was not administered as study was terminated before completion of Part A of the dose escalation period.

Participants were not enrolled in to this arm, as trial was terminated in dose escalation phase.

LY3435151

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

The reason for this study is to see if the study drug LY3435151 is safe in participants with advanced solid tumors.

A Study of LY3435151 in Participants With Solid Tumors

A Phase 1a/1b Study of LY3435151 Administered to Patients With Advanced Solid Tumors

A DLT is defined as an Adverse Event that is likely related to the study medication or combination, and fulfills any one of the following criteria, graded according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0:

1. Any death not clearly due to the underlying disease or extraneous causes
2. Neutropenic fever 2. Any Grade ≥3 non-hematologic toxicity
3. Grade ≥4 neutropenia or thrombocytopenia \>7 days
4. Grade ≥3 thrombocytopenia with bleeding
5. Grade ≥3 nausea/vomiting or diarrhea\>72 hours with adequate antiemetic and other supportive care
6. Grade ≥3 fatigue ≥1 week
7. Grade ≥3 electrolyte abnormality that lasts\>72 hours, unless the Participant has clinical symptoms, in which case all Grade 3+electrolyte abnormality regardless of duration should count as a DLT
8. Grade ≥3 prolongation of QT interval corrected using the Fridericia formula on 2 separate electrocardiogram readings approximately 5 min apart.

Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3435151.

PK: Cmax of LY3435151 in Combination with Pembrolizumab.

Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants per cohort with at least 1 measurable lesion, multiplied by 100.

Disease Control Rate (DCR) is the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

DOR is the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Time to response (TTR) is defined as the time from the date of start of treatment to the date measurement criteria for confirmed CR or PR (whichever is first recorded) are first met. For participants who are not known to have achieved CR or PR as of the data inclusion cut-off date, TTR will be censored at the date of the last objective disease assessment prior the date of any subsequent systematic anticancer therapy.

PFS time was measured from the date of randomization until the first radiographic documentation of progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.

Eli Lilly and Company

Participants received 10 mg dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.

10 mg LY3435151

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Japan

Region of Enrollment

This study was terminated before completion of the dose escalation phase (Part A), due to strategic business decision made by the company.

Chief Medical Officer

Zero participants were analyzed. This outcome was not determined because the study terminated before completion of Part A of the dose escalation period.

Number of Participants With LY3435151 Dose-Limiting Toxicities (DLTs)

All randomized participants who received at least one dose of study drug and had evaluable PK data.

Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3435151

Zero participants were analyzed. The study was terminated early and no data was collected.

PK: Cmax of LY3435151 in Combination With Pembrolizumab

Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR)

Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and Stable Disease

Duration of Response (DoR)

Time to Response (TTR)

Progression Free Survival (PFS)

Participants received 10 milligrams (mg) dose of LY3435151 via intravenous (IV) as an IV push or IV bolus infusion.

Spots Global Cancer Trial Database for high grade serous ovarian carcinoma