CancerPhase 1NCT03495323
A Study of Prexasertib (LY2606368), CHK1 Inhibitor, and LY3300054, PD-L1 Inhibitor, in Patients With Advanced Solid Tumors
A Phase 1 study testing LY3300054 and Prexasertib in people with Cancer, run by Dana-Farber Cancer Institute at 1 site in United States.
Trial summary
This research study is studying a combination of a targeted therapy and an immune therapy as a possible treatment. The drugs involved in this study are: Prexasertib (LY2606368) LY3300054 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- LY3300054 and Prexasertib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 16 May 2018to 1 Feb 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent obtained prior to any study-specific procedures not considered part of routine medical care.
- Patients must have histologically confirmed solid tumor that is metastatic or unresectable, and there is no available therapy likely to convey clinical benefit
- Patients must have measurable disease by RECIST version 1.1. Measurable disease is defined as at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20mm (≥ 2cm) with conventional techniques or as ≥ 10mm (≥ 1cm) with spiral computed tomography (CT) scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease.
- Patients must have recovered to eligibility levels from prior toxicity or adverse events as a result of previous treatment prior to entering the study (except alopecia).
- Age ≥18 years, as no dosing or adverse event data are currently available on the use of prexasertib in combination with LY3300054 in patients < 18 years of age, children are excluded from this study.
- ECOG performance status 0-1.
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- Patients must have normal organ and marrow function as defined below:
- absolute neutrophil count ≥ 1,500/mcL
- platelets ≥ 100,000/mcL
- total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)
- AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN
- creatinine ≤ 1.5 × institutional ULN OR
- creatinine clearance ≥ 60 mL/min by Cockcroft-Gault equation for participants with creatinine levels above institutional normal.
- Free T4 within institutional normal limits
- The effects of prexasertib and LY3300054 on the developing human fetus are unknown. For this reason, women of childbearing potential and male patients with partners of childbearing potential must agree to use two highly effective forms of contraception (see Section 5.5.1) prior to study entry, for the duration of study participation, and for 6 months after completion of study. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and for 3 months after completion of prexasertib and LY3300054 administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
- Women of childbearing potential enrolling on study must have a negative serum pregnancy test prior to registration.
- Childbearing potential is defined as women who are not postmenopausal (defined as amenorrheic for ≥ 12 months following cessation of any exogenous hormonal treatments; LH and FSH levels in the postmenopausal range for women under 50; radiation-induced oophorectomy with last menses > 12 months prior; or chemotherapy-induced menopause with last menses > 12 months prior) or surgically sterile (bilateral oophorectomy or hysterectomy).
- Ability to understand and the willingness to sign a written informed consent document. Patients must be willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
Who cannot join
- Participants who have had chemotherapy, immune therapy, or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C; five-half lives for any investigational or FDA-approved kinase inhibitors) prior to entering the study. Patients who have received prior CHK1 inhibitor therapy are excluded. Exposure to prior PD-L1 antibody will be allowed as long as this was not the most recent treatment prior to enrollment.
- No prior radiation to > 25% of the marrow
- Must not have received more than 4 lines of cytotoxic chemotherapy. A line of therapy is defined as being preceded by disease progression. Discontinuation of a regimen without progression (for example, due to toxicity) or a switch of an agent within the same drug class (for example from cisplatin to carboplatin) will not be considered a new line of therapy. Similarly, maintenance therapy (continuation maintenance or switch maintenance) will not be considered a new line of treatment.
- Participants who are receiving any other investigational agents.
- Participants who have undergone major surgery within 14 days of starting the study treatment, or participants who have not recovered to baseline status from the effects of major surgery received more than 14 days prior.
- Participants with known brain metastases or carcinomatous meningitis are excluded from this clinical trial, with the exception of patients with brain metastatic disease that has previously been treated and remained stable on MRI ≥ 2 months prior to enrollment, without steroids or anti-epileptic medications. These patients may be enrolled at the discretion of the Principal Investigator.
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- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled seizures, myocardial infarction within the past 3 months, superior vena cava syndrome, unstable spinal cord compression (untreated and unstable for at least 28 days prior to study entry), or psychiatric illness/social situations that would limit compliance with study requirements.
- Participants must not have experienced a Grade ≥ 3 immune-related AE or an immune-related neurologic or ocular AE of any grade while receiving prior immunotherapy, or experienced a toxicity of any grade that led to permanent discontinuation of prior immunotherapy as a result of the toxicity. Participants with prior endocrine adverse events of Grade ≤ 2 are permitted to enroll if stably maintained on appropriate replacement therapy and are asymptomatic. In the setting of prior immune-related AE, participants must not have required the use of additional immunosuppressive agents other than corticosteroids for the management of the adverse event(s), not have experienced recurrence of the adverse event if re-challenged, and not currently requiring maintenance doses of > 10 mg of prednisone or equivalent per day at the time of enrollment.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to prexasertib or LY3300054.
- The effects of prexasertib and LY3300054 on the developing human fetus are unknown. For this reason, pregnant women are excluded from this study. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with prexasertib and LY3300054, breastfeeding women are also excluded.
- Known HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with prexasertib and LY3300054. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy such as prexasertib.
- Participants with known active or chronic infection with Hepatitis B or C.
- Consistent QTc > 470 msec on more than one screening ECG. Patients with a history of long QTc syndrome or personal or family history of ventricular arrhythmias will be excluded
Trial locations and contacts
1 site in 1 country.
United States1 site
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
About this study
Official title: A Phase I Combination Study of Prexasertib (LY2606368), CHK1 Inhibitor, and LY3300054, PD-L1 Inhibitor, in Patients With Advanced Solid Tumors
This research study is studying a combination of a targeted therapy and an immune therapy as a possible treatment.
The drugs involved in this study are:
- Prexasertib (LY2606368)
- LY3300054
Read the detailed description
This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate doses of the investigational drugs to use for further studies. "Investigational" means that the drugs are being studied.
The FDA (the U.S. Food and Drug Administration) has not approved prexasertib or LY3300054 as a treatment for any disease.
Prexasertib (LY2606368) is a checkpoint kinase 1 (CHK1) inhibitor that is being developed as a treatment for patients with advanced cancer. CHK1 inhibitors work by preventing the cancer cells from being able to repair damaged DNA (one of the building blocks of a cell) which then leads to cell death.
A monoclonal antibody is a protein that is made in a laboratory that can target specific substances in the body. LY3300054 is a monoclonal antibody that targets programmed cell death ligand 1 (PD-L1). PD-L1 is a protein often produced by cancer cells or surrounding cells that stops white blood cells from attacking the cancer cells. The drug blocks the protein, allowing the immune system to recognize and attack the cancer cells.
- Conditions
- Cancer
- Being tested
- LY3300054, Prexasertib
- Keywords
- Cancer Care
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LY3300054Drug
LY3300054 is a monoclonal antibody that targets programmed cell death ligand 1 (
PrexasertibDrug
Prexasertib work by preventing the cancer cells from being able to repair damaged DNA (one of the building blocks of a cell) which then leads to cell death
| Study group | Role | What they receive |
|---|---|---|
| Prexasertib + LY3300054 | Experimental | * Prexasertib is administered intravenously twice per cycle
* LY3300054 is administered intravenously twice per cycle Receives: Drug: LY3300054; Drug: Prexasertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose Limiting Toxicity
Measured: 2 years
Secondary outcomes (8)
Pharmacokinetics of prexasertib and LY3300054
Pharmacokinetic Sampling - Peak Plasma Concentration (Cmax)
Measured: 2 years
Pharmacokinetics of prexasertib and LY3300054
Pharmacokinetic Sampling - Area Under the Plasma Concentration versus Time Curve (AUC)
Measured: 2 years
Changes in PD-L1 expression in paired pre- and on-treatment biopsies
Measured: 2 years
H2AX expression levels in paired tumor biopsies as a consequence of treatment with prexasertib as proof-of-principle of target engagement
Measured: 2 years
Changes in immune markers through analysis of T-cell subsets in paired tumor biopsies
Measured: 2 years
Changes in cytokine profile in peripheral blood samples
Measured: 2 years
Changes in immune markers through analysis of T-cell subsets in peripheral blood and tumor tissue
Measured: 2 years
Differences in immune markers between responders and non-responders
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2018
- Study start16 May 2018
- Primary completion1 Feb 2021
- Study completion1 Feb 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Principal investigator, Geoffrey Shapiro, MD, PhD, Dana-Farber Cancer Institute
- Investigators
- Geoffrey T Shapiro, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03495323
- Sponsor's protocol ID
- 18-008
- Status last verified
- Apr 2021
- First submitted
- 29 Mar 2018
- Last updated
- 15 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Do KT, Manuszak C, Thrash E, Giobbie-Hurder A, Hu J, Kelland S, Powers A, de Jonge A, Shapiro GI, Severgnini M. Immune modulating activity of the CHK1 inhibitor prexasertib and anti-PD-L1 antibody LY3300054 in patients with high-grade serous ovarian cancer and other solid tumors. Cancer Immunol Immunother. 2021 Oct;70(10):2991-3000. doi: 10.1007/s00262-021-02910-x. Epub 2021 Mar 20.
PubMed 33745032
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Combination Study of Prexasertib (LY2606368), CHK1 Inhibitor, and LY3300054, PD-L1 Inhibitor, in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03495323
- Acronym / sponsor ID
- 18-008
- Conditions
- Cancer
- Keywords
- Cancer Care
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- Study start
- 16 May 2018 (actual)
- Primary completion
- 1 Feb 2021 (actual)
- Study completion
- 1 Feb 2021 (actual)
- First posted
- 12 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is studying a combination of a targeted therapy and an immune therapy as a possible treatment.
The drugs involved in this study are:
- Prexasertib (LY2606368)
- LY3300054
Detailed description
This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate doses of the investigational drugs to use for further studies. "Investigational" means that the drugs are being studied.
The FDA (the U.S. Food and Drug Administration) has not approved prexasertib or LY3300054 as a treatment for any disease.
Prexasertib (LY2606368) is a checkpoint kinase 1 (CHK1) inhibitor that is being developed as a treatment for patients with advanced cancer. CHK1 inhibitors work by preventing the cancer cells from being able to repair damaged DNA (one of the building blocks of a cell) which then leads to cell death.
A monoclonal antibody is a protein that is made in a laboratory that can target specific substances in the body. LY3300054 is a monoclonal antibody that targets programmed cell death ligand 1 (PD-L1). PD-L1 is a protein often produced by cancer cells or surrounding cells that stops white blood cells from attacking the cancer cells. The drug blocks the protein, allowing the immune system to recognize and attack the cancer cells.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Prexasertib + LY3300054 | Experimental | Drug: LY3300054, Drug: Prexasertib* Prexasertib is administered intravenously twice per cycle * LY3300054 is administered intravenously twice per cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Written informed consent obtained prior to any study-specific procedures not considered part of routine medical care.
- Patients must have histologically confirmed solid tumor that is metastatic or unresectable, and there is no available therapy likely to convey clinical benefit
- Patients must have measurable disease by RECIST version 1.1. Measurable disease is defined as at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20mm (≥ 2cm) with conventional techniques or as ≥ 10mm (≥ 1cm) with spiral computed tomography (CT) scan, MRI, or calipers by clinical exam. See Section 11 for the evaluation of measurable disease.
- Patients must have recovered to eligibility levels from prior toxicity or adverse events as a result of previous treatment prior to entering the study (except alopecia).
- Age ≥18 years, as no dosing or adverse event data are currently available on the use of prexasertib in combination with LY3300054 in patients < 18 years of age, children are excluded from this study.
Key exclusion criteria (13 listed)
- Participants who have had chemotherapy, immune therapy, or radiotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C; five-half lives for any investigational or FDA-approved kinase inhibitors) prior to entering the study. Patients who have received prior CHK1 inhibitor therapy are excluded. Exposure to prior PD-L1 antibody will be allowed as long as this was not the most recent treatment prior to enrollment.
- No prior radiation to > 25% of the marrow
- Must not have received more than 4 lines of cytotoxic chemotherapy. A line of therapy is defined as being preceded by disease progression. Discontinuation of a regimen without progression (for example, due to toxicity) or a switch of an agent within the same drug class (for example from cisplatin to carboplatin) will not be considered a new line of therapy. Similarly, maintenance therapy (continuation maintenance or switch maintenance) will not be considered a new line of treatment.
- Participants who are receiving any other investigational agents.
- Participants who have undergone major surgery within 14 days of starting the study treatment, or participants who have not recovered to baseline status from the effects of major surgery received more than 14 days prior.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LY3300054LY3300054 is a monoclonal antibody that targets programmed cell death ligand 1 ( | Drug | Prexasertib + LY3300054 |
| PrexasertibPrexasertib work by preventing the cancer cells from being able to repair damaged DNA (one of the building blocks of a cell) which then leads to cell death | Drug | Prexasertib + LY3300054 |
Primary outcome
Dose Limiting Toxicity
Time frame: 2 years
8 secondary outcomes
Pharmacokinetics of prexasertib and LY3300054
Time frame: 2 years
Pharmacokinetics of prexasertib and LY3300054
Time frame: 2 years
Changes in PD-L1 expression in paired pre- and on-treatment biopsies
Time frame: 2 years
H2AX expression levels in paired tumor biopsies as a consequence of treatment with prexasertib as proof-of-principle of target engagement
Time frame: 2 years
Changes in immune markers through analysis of T-cell subsets in paired tumor biopsies
Time frame: 2 years
Changes in cytokine profile in peripheral blood samples
Time frame: 2 years
Changes in immune markers through analysis of T-cell subsets in peripheral blood and tumor tissue
Time frame: 2 years
Differences in immune markers between responders and non-responders
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2021.
- Derived from this study: PubMed 33745032Do KT, Manuszak C, Thrash E, Giobbie-Hurder A, Hu J, Kelland S, Powers A, de Jonge A, Shapiro GI, Severgnini M. Immune modulating activity of the CHK1 inhibitor prexasertib and anti-PD-L1 antibody LY3300054 in patients with high-grade serous ovarian cancer and other solid tumors. Cancer Immunol Immunother. 2021 Oct;70(10):2991-3000. doi: 10.1007/s00262-021-02910-x. Epub 2021 Mar 20.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Geoffrey T Shapiro, MD principal investigator
Dana-Farber Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LY3300054 and Prexasertib in people with Cancer, run by Dana-Farber Cancer Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose Limiting Toxicity (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03495323, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2021.