Advanced Cancer
Conditions
Keywords
PD-1, PD-L1
Brief summary
The main purpose of this study is to evaluate the safety and tolerability of the study drug LY3434172, a PD-1/PD-L1 bispecific antibody, in participants with advanced solid tumors.
Interventions
DRUGLY3434172
Administered IV
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have histological or cytological evidence of a diagnosis of cancer that is not amenable/resistant to approved standard-of-care therapy for the following solid tumors: Melanoma, non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), urothelial cancer, gastric cancer, colorectal cancer, biliary tract cancer, anal cancer, nasopharyngeal cancer, esophageal cancer, SCLC, ovarian cancer, mesothelioma, pan-tumor MSIhi solid tumors, hepatocellular carcinoma, merkel cell cancer, cutaneous squamous cell carcinoma, endometrial cancer, breast cancer, cervical cancer, thyroid cancer, salivary cancer, and prostate cancer who have received at least one line of standard systemic therapy for their respective tumor type in the metastatic setting with progressive locally advanced or metastatic disease. Prior anti-programmed death 1 (PD-1) and anti-programmed death ligand 1 (PD-L1) allowed if they received another therapy immediately prior to this study or there has been a lapse of approximately ≥90 days from prior therapy. * Must be willing to undergo pretreatment and on-treatment core needle or excisional tumor biopsies. * Have at least one measurable lesion assessable as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. * Have adequate organ function. * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale. * Have an estimated life expectancy of 12 weeks, in the judgment of the investigator.
Exclusion criteria
* Have symptomatic central nervous system (CNS) malignancy or metastasis not requiring concurrent treatment, including but not limited to surgery, radiation, corticosteroids and/or anticonvulsants to treat CNS metastases, and their disease is asymptomatic and radiographically stable for at least 30 days. * Have moderate or severe cardiovascular disease. * Have active or suspected autoimmune disease (eg. autoimmune vasculitis, autoimmune myocarditis, among others). * Have serious concomitant systemic disorder that would compromise the participant's ability to adhere to the protocol, including known infection with human immunodeficiency virus (HIV) unless they are well controlled on highly active antiretroviral therapy (HAART) therapy with no evidence of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections within the last 2 years, and CD4 T-cells count \> 350 cells/µl , active hepatitis B virus (HBV), active hepatitis C virus (HCV), active autoimmune disorders, or prior documented severe autoimmune or inflammatory disorders requiring immunosuppressive treatment. * Use of escalating or chronic supraphysiologic doses of corticosteroids or immunosuppressive agents (such as, exceeding 10 milligrams/day of prednisone or equivalent). Use of topical, ophthalmic, inhaled, and intranasal corticosteroids permitted. * Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea. * Evidence of interstitial lung disease or noninfectious pneumonitis (active or treated by corticosteroid therapy).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | Baseline through Cycle 1 (Up to 42 Day Cycle) | A DLT is defined as adverse event/s of grade 3 or higher that occurs during the DLT observation period, which is Cycle 1 of each dose escalation cohort, and is clinically significant and definitely, probably, or possibly related to LY3434172, in the opinion of the investigator. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK: Maximum Concentration (Cmax) of LY3434172 | PK: Cycle 1 Day 1 (C1D1): Predose; 1 hour(h); 3 h; 24 h; 72 h; 168 h post-infusion; C1D15: Predose; 1 h; 3 h; 24 h; 72 h; 168 h post-infusion | PK: Cmax of LY3434172 |
| PK: Area Under the Curve From Zero to Time to Last Measurable Concentration (AUC0-tlast) of LY3434172 | PK: Cycle 1 Day 1 (C1D1): Predose; 1 hour(h); 3 h; 24 h; 72 h; 168 h post-infusion; C1D15: Predose; 1 h; 3 h; 24 h; 72 h; 168 h post-infusion | PK: AUC 0-tlast of LY3434172 |
| Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR) | Baseline through Measured Progressive Disease (Up to 8.4 Months) | ORR: Percentage of participants who have received any amount of study drug, have at least one postbaseline tumor image, and achieved a best overall response (BOR) of confirmed Complete Response (CR) is defined a disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). Partial Response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3434172 | PK: Cycle 1 Day 1 (C1D1): Predose; 1 hour(h); 3 h; 24 h; 72 h; 168 h post-infusion; Cycle 1 Day 15 (C1D15): Predose; 1 h; 3 h; 24 h; 72 h; 168 h post-infusion | PK: Cmin of LY3434172 |
| Time to Response (TTR) | Baseline to Date of CR or PR (Up to 8.4 Months) | TTR is defined as the time from the date of first study treatment until the first evidence of confirmed CR or PR. |
| Disease Control Rate (DCR): Percentage of Participants Who Exhibit Stable Disease (SD), CR or PR | Baseline through Measured Progressive Disease (Up to 8.4 Months) | Disease control rate is defined as the number of participants with SD, confirmed PR, or confirmed CR (CR+PR+SD) divided by the number of enrolled participants who have received any quantity of study treatment. |
| Duration of Response (DOR) | Date of CR or PR to Date of Objective Progression or Death Due to Any Cause (Up to 8.4 Months) | DOR is defined only for responders (participants with a confirmed CR or PR). It is measured from the date of first evidence of a confirmed CR or PR to the date of the first observed radiographically documented progressive disease (PD), or the date of death due to any cause, whichever is earlier. If a responder is not known to have died or have objective progression as of the data inclusion cutoff date, DoR will be censored at the date of the last complete objective progression-free disease assessment. |
Countries
Australia, Belgium, France, South Korea, United States
Participant flow
Pre-assignment details
Completers are defined as participants who were observed for both primary and secondary outcomes.
Participants by arm
| Arm | Count |
|---|---|
| 3 mg - 10 mg LY3434172 3 mg LY3434172 administered IV on Day 1 Cycle 1 of 28-day cycle. 10 mg LY3434172 administered IV on Day 15 Cycle 1 of 28-day cycle. Participants continued to receive study treatment until they met a criterion for discontinuation. | 3 |
| 30 mg LY3434172 30 mg LY3434172 administered IV on Day 1 and Day 15 of 28-day cycle. Participants continued to receive study treatment until they met a criterion for discontinuation. | 4 |
| 100 mg LY3434172 100 mg LY3434172 administered IV on Day 1 and Day 15 of 28-day cycle. Participants continued to receive study treatment until they met a criterion for discontinuation. | 3 |
| Total | 10 |
Baseline characteristics
| Characteristic | 3 mg - 10 mg LY3434172 | 30 mg LY3434172 | 100 mg LY3434172 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 2 Participants | 3 Participants | 1 Participants | 6 Participants |
| Region of Enrollment Australia | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Belgium | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Region of Enrollment South Korea | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 2 Participants | 3 Participants | 0 Participants | 5 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 1 Participants | 6 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 1 / 4 | 2 / 3 |
| other Total, other adverse events | 3 / 3 | 4 / 4 | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 | 1 / 4 | 1 / 3 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT is defined as adverse event/s of grade 3 or higher that occurs during the DLT observation period, which is Cycle 1 of each dose escalation cohort, and is clinically significant and definitely, probably, or possibly related to LY3434172, in the opinion of the investigator.
Time frame: Baseline through Cycle 1 (Up to 42 Day Cycle)
Population: All participants who received any quantity of LY3434172, regardless of their eligibility for the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 3 mg - 10 mg LY3434172 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| 30 mg LY3434172 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| 100 mg LY3434172 | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
Secondary
Disease Control Rate (DCR): Percentage of Participants Who Exhibit Stable Disease (SD), CR or PR
Disease control rate is defined as the number of participants with SD, confirmed PR, or confirmed CR (CR+PR+SD) divided by the number of enrolled participants who have received any quantity of study treatment.
Time frame: Baseline through Measured Progressive Disease (Up to 8.4 Months)
Population: All participants who received any quantity of LY3434172, regardless of their eligibility for the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 3 mg - 10 mg LY3434172 | Disease Control Rate (DCR): Percentage of Participants Who Exhibit Stable Disease (SD), CR or PR | 66.7 percentage of participants |
| 30 mg LY3434172 | Disease Control Rate (DCR): Percentage of Participants Who Exhibit Stable Disease (SD), CR or PR | 25.0 percentage of participants |
| 100 mg LY3434172 | Disease Control Rate (DCR): Percentage of Participants Who Exhibit Stable Disease (SD), CR or PR | 66.7 percentage of participants |
Secondary
Duration of Response (DOR)
DOR is defined only for responders (participants with a confirmed CR or PR). It is measured from the date of first evidence of a confirmed CR or PR to the date of the first observed radiographically documented progressive disease (PD), or the date of death due to any cause, whichever is earlier. If a responder is not known to have died or have objective progression as of the data inclusion cutoff date, DoR will be censored at the date of the last complete objective progression-free disease assessment.
Time frame: Date of CR or PR to Date of Objective Progression or Death Due to Any Cause (Up to 8.4 Months)
Population: All participants who received any quantity of LY3434172, regardless of their eligibility for the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 mg LY3434172 | Duration of Response (DOR) | NA Months |
Secondary
Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR)
ORR: Percentage of participants who have received any amount of study drug, have at least one postbaseline tumor image, and achieved a best overall response (BOR) of confirmed Complete Response (CR) is defined a disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). Partial Response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Baseline through Measured Progressive Disease (Up to 8.4 Months)
Population: All participants who received any quantity of LY3434172, regardless of their eligibility for the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 3 mg - 10 mg LY3434172 | Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR) | Complete Response | 0 Percentage of participants |
| 3 mg - 10 mg LY3434172 | Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR) | Partial Response | 0 Percentage of participants |
| 30 mg LY3434172 | Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR) | Complete Response | 0 Percentage of participants |
| 30 mg LY3434172 | Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR) | Partial Response | 0 Percentage of participants |
| 100 mg LY3434172 | Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR) | Complete Response | 0 Percentage of participants |
| 100 mg LY3434172 | Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR) | Partial Response | 33.3 Percentage of participants |
Secondary
Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3434172
PK: Cmin of LY3434172
Time frame: PK: Cycle 1 Day 1 (C1D1): Predose; 1 hour(h); 3 h; 24 h; 72 h; 168 h post-infusion; Cycle 1 Day 15 (C1D15): Predose; 1 h; 3 h; 24 h; 72 h; 168 h post-infusion
Population: All participants who received at least one dose of LY3434172 and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 3 mg - 10 mg LY3434172 | Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3434172 | Cycle 1 Day 1 | NA nanogram per milliliter (ng/mL) | — |
| 3 mg - 10 mg LY3434172 | Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3434172 | Cycle 1 Day 15 | NA nanogram per milliliter (ng/mL) | — |
| 30 mg LY3434172 | Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3434172 | Cycle 1 Day 1 | 775 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 107 |
| 30 mg LY3434172 | Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3434172 | Cycle 1 Day 15 | 1017 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 63 |
| 100 mg LY3434172 | Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3434172 | Cycle 1 Day 1 | 4150 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 254 |
| 100 mg LY3434172 | Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3434172 | Cycle 1 Day 15 | 5600 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 85 |
Secondary
PK: Area Under the Curve From Zero to Time to Last Measurable Concentration (AUC0-tlast) of LY3434172
PK: AUC 0-tlast of LY3434172
Time frame: PK: Cycle 1 Day 1 (C1D1): Predose; 1 hour(h); 3 h; 24 h; 72 h; 168 h post-infusion; C1D15: Predose; 1 h; 3 h; 24 h; 72 h; 168 h post-infusion
Population: All participants who received at least one dose of LY3434172 and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 3 mg - 10 mg LY3434172 | PK: Area Under the Curve From Zero to Time to Last Measurable Concentration (AUC0-tlast) of LY3434172 | C1D1 | 7280 hour*nanogram per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 51 |
| 3 mg - 10 mg LY3434172 | PK: Area Under the Curve From Zero to Time to Last Measurable Concentration (AUC0-tlast) of LY3434172 | C1D15 | NA hour*nanogram per milliliter (hr*ng/mL) | — |
| 30 mg LY3434172 | PK: Area Under the Curve From Zero to Time to Last Measurable Concentration (AUC0-tlast) of LY3434172 | C1D1 | 584000 hour*nanogram per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 31.5 |
| 30 mg LY3434172 | PK: Area Under the Curve From Zero to Time to Last Measurable Concentration (AUC0-tlast) of LY3434172 | C1D15 | 559000 hour*nanogram per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 239 |
| 100 mg LY3434172 | PK: Area Under the Curve From Zero to Time to Last Measurable Concentration (AUC0-tlast) of LY3434172 | C1D1 | 1900000 hour*nanogram per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 121 |
| 100 mg LY3434172 | PK: Area Under the Curve From Zero to Time to Last Measurable Concentration (AUC0-tlast) of LY3434172 | C1D15 | 3010000 hour*nanogram per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 19.9 |
Secondary
PK: Maximum Concentration (Cmax) of LY3434172
PK: Cmax of LY3434172
Time frame: PK: Cycle 1 Day 1 (C1D1): Predose; 1 hour(h); 3 h; 24 h; 72 h; 168 h post-infusion; C1D15: Predose; 1 h; 3 h; 24 h; 72 h; 168 h post-infusion
Population: All participants who received at least one dose of LY3434172 and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 3 mg - 10 mg LY3434172 | PK: Maximum Concentration (Cmax) of LY3434172 | Cycle 1 Day 15 | NA ng/mL | — |
| 3 mg - 10 mg LY3434172 | PK: Maximum Concentration (Cmax) of LY3434172 | Cycle 1 Day 1 | 734 ng/mL | Geometric Coefficient of Variation 19.1 |
| 30 mg LY3434172 | PK: Maximum Concentration (Cmax) of LY3434172 | Cycle 1 Day 1 | 8250 ng/mL | Geometric Coefficient of Variation 17.7 |
| 30 mg LY3434172 | PK: Maximum Concentration (Cmax) of LY3434172 | Cycle 1 Day 15 | 18600 ng/mL | Geometric Coefficient of Variation 52.9 |
| 100 mg LY3434172 | PK: Maximum Concentration (Cmax) of LY3434172 | Cycle 1 Day 1 | 22700 ng/mL | Geometric Coefficient of Variation 60.8 |
| 100 mg LY3434172 | PK: Maximum Concentration (Cmax) of LY3434172 | Cycle 1 Day 15 | 43000 ng/mL | Geometric Coefficient of Variation 58.5 |
Secondary
Time to Response (TTR)
TTR is defined as the time from the date of first study treatment until the first evidence of confirmed CR or PR.
Time frame: Baseline to Date of CR or PR (Up to 8.4 Months)
Population: All participants who received any quantity of LY3434172, regardless of their eligibility for the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 100 mg LY3434172 | Time to Response (TTR) | NA Months |