CancerPhase 2NCT04534283
A Basket Trial of an ERK1/2 Inhibitor (LY3214996) in Combination With Abemaciclib.
A Phase 2 study testing Abemaciclib and LY3214996 in people with Cancer and Cancer Metastatic, run by Anita Turk at 1 site in United States.
Trial summary
The purpose of CTO-IUSCC-0730 study is to assess the clinical efficacy of LY3214996 in combination with abemaciclib at the recommended phase 2 dose of LY3214996 200 mg orally daily and abemaciclib 150 mg orally twice daily. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Cancer Metastatic, BRAF V600E
- What is being tested?
- Abemaciclib and LY3214996
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Oct 2020to 7 Aug 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Have a histological or cytological diagnosis of advanced unresectable or metastatic cancer (American Joint Committee on Cancer Staging Criteria) (Edge et al. 2009).
- 2. The patient must be, in the judgement of the investigator, an appropriate candidate for experimental therapy, either after available standard therapies (per available local guidelines) have failed to provide clinical benefit for their disease or after the patient has refused standard treatments.
- 3. Have one of the following alterations as defined below using a CLIA-certified next-generation sequencing test:
- Point mutation in BRAF, RAF1, MEK1/2, or ERK1/2 that have been previously characterized to be gain-of-function mutations. These mutations have to be specified as gain-of-function as listed in the OncoKB and/or JAX-CKB databases. i. Patients with NSCLC that harbor BRAF V600E treated with prior RAF and/or MEK inhibition therapy will be excluded.
- Patients with tumor types other than NSCLC that harbor BRAF V600E mutations who have been treated and progressed on prior BRAF and/or MEK inhibition will be included.
- Patients with NSCLC that harbor BRAF V600E will only be enrolled if they are not a candidate for FDA approved therapy
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- Amplification of RAF1 defined as >6 copies of the respective gene.
- Gene fusion in which BRAF, RAF1, MEK1/2, or ERK1/2, is a fusion partner; in which the fusion is determined to be in-frame; and the kinase domain of BRAF, RAF1, MEK1/2, or ERK1/2 is retained.
- Point mutations, frameshift insertions/deletions, splice site mutations, or stop gain mutations that results in loss-of-function of NF1.
- 4. Have measurable disease amenable to biopsy. If biopsy is deemed unsafe at time of procedure, patients will remain eligible for study.
- 5. Must be able to provide written informed consent and HIPAA authorization for release of personal health information.
- 6. Have a performance status (PS) of 0 or 1 on the Eastern Cooperative Oncology (Group (ECOG) scale (Oken et al. 1982) within 21 (+/-7) days prior to registration for protocol therapy.
- 7. Have discontinued previous systemic treatments > 3 weeks for cancer prior to first dose of investigational therapy. Patient must have resolution, except for alopecia, of all clinically significant toxic effects of prior chemotherapy, surgery, or radiotherapy to Grade ≤1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0.
- 8. Have adequate organ function, as defined below: Laboratory Value (Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; ANC = absolute neutrophil count; ULN = upper limit of normal.) Hematologic ANC ≥1.5 × 109/L Platelets ≥100 × 109/L Hemoglobin ≥9.0 g/dL Transfusions to increase the patient's hemoglobin level to 9 g/dL are not permitted within 1 week prior to the baseline hematology profile Hepatic Total bilirubin ≤1.5 × ULN OR <2.0 mg/dL in patients with Gilbert's disease ALT and AST ≤2.5 × ULN OR ≤5 × ULN if the liver has tumor involvement Renal Serum creatinine OR Calculated creatinine clearance (see Appendix 3) ≤1.5 × ULN OR ≥50 mL/min
- 9. Are at least 18 years old at the time of screening.
- 10. Are male patients who are sterile (including vasectomy confirmed by post vasectomy semen analysis), or agree to use an effective method of contraception and not to donate sperm, or who practice total abstinence from heterosexual activity, starting with the first dose of study treatment, during the study, and for at least 6 months following the last dose of study treatment.
- 11. Are female patients of non-childbearing potential (surgically sterile after having a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy or postmenopausal), or are female patients of child-bearing potential who are not pregnant, as confirmed by a serum pregnancy test within 14 (+/-7) days prior to receiving first dose of study treatment and who agree to use 2 methods of birth control (hormonal or intrauterine plus a barrier method) or practice total abstinence from heterosexual activity during the study for at least 6 months following the last dose of the study treatment.
- 12. Are able to swallow capsules or tablets 13. Have an estimated life expectancy of ≥12 weeks, in the judgment of the investigator.
Who cannot join
- Have a serious concomitant systemic disorder (for example, active infection or a gastrointestinal disorder causing clinically significant symptoms such as nausea, vomiting or diarrhea, or profound immune suppression) that, in the opinion of the investigator, would compromise the patient's ability to adhere to the protocol.
- Have or known activated/reactivated hepatitis A, B, or C (screening is not required).
- Uncontrolled human immunodeficiency virus (HIV) infection are considered ineligible. HIV- infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- Known HIV positive patients who meet the following criteria will be considered eligible:
- CD4 count ≥ 350 cells/mm3
- Undetectable viral load
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- Maintained on modern therapeutic regimens utilizing non-CYP interactive agents (i.e. excluding ritonavir)
- No history of AIDS-defining opportunistic infections
- Have symptomatic and untreated central nervous system (CNS) malignancy or metastasis (screening is not required).
- Patients with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids for their CNS metastasis and/or anticonvulsants. Patient must be > 4 weeks from therapy completion (including radiation and/or surgery) and clinically stable at time of study entry. Brain MRI or head CT is required at screening for patients with known brain metastases.
- Have current hematologic malignancies, acute or chronic leukemia
- Have a second primary malignancy that in the judgment of the principle investigator may affect the interpretation of results
- Have prior malignancies within the last 3 years prior to study enrollment. Patients with carcinoma in situ of any origin and patients with prior malignancies who completed curative intent-treatment and whose likelihood of recurrence is very low, as judged by the principal investigator, will remain eligible for this study. The principal investigator will approve enrollment of patients with prior malignancies in remission before these patients are enrolled.
- Are currently enrolled in a clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study
- Have participated, within the last 28 days in a clinical trial involving an investigational product.
- Have previously completed or withdrawn from this study or any other study investigating an ERK1/2 inhibitor.
- Had prior therapy with an ERK1/2 inhibitor.
- Had prior chemotherapy within 3 weeks of study registration.
- Had prior non-CNS radiation within 2 weeks of study registration. Please refer to exclusion criteria #4 for patients who have required radiation for CNS disease.
- If female, is pregnant, breastfeeding, or planning to become pregnant.
- Currently using concomitant medications that are strong inhibitors or inducers of CYP3A4.
- Have serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study.
- This includes cardiogenic syncope, ventricular arrhythmias, history of sudden cardiac arrest, or severe dyspnea at rest or requiring oxygen therapy.
- This includes patients with any evidence of interstitial lung disease (ILD) (not just serious and/or uncontrolled ILD) and any history of severe ILD.
Trial locations and contacts
1 site in 1 country.
United States1 site
Indiana University Hospital / IU Simon Cancer Center
Indianapolis, Indiana, 46202
About this study
Official title: A Phase 2 Basket Trial of an ERK1/2 Inhibitor (LY3214996) in Combination With Abemaciclib for Patients Whose Tumors Harbor Pathogenic Alterations in BRAF, RAF1, MEK1/2, ERK1/2, and NF1.
The purpose of CTO-IUSCC-0730 study is to assess the clinical efficacy of LY3214996 in combination with abemaciclib at the recommended phase 2 dose of LY3214996 200 mg orally daily and abemaciclib 150 mg orally twice daily. Patients will be treated until evidence of disease progression, non-compliance with study protocol, unacceptable major toxicity, at subject's own request for withdrawal, or if the study closes for any reason.
- Conditions
- Cancer, Cancer Metastatic, BRAF V600E, MEK1 Gene Mutation, MEK2 Gene Mutation, ERK Mutation
- Being tested
- Abemaciclib, LY3214996
- Keywords
- Point Mutation, Metastatic Cancer, Advanced Cancer
- Medical subject headings
- Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AbemaciclibDrug
Also called LY2835219
Subjects will receive Abemaciclib 150 mg orally twice daily until disease progression, unacceptable toxicity, or patient preference to withdraw from study.
LY3214996Drug
Subjects will recieve LY3214996 200 mg orally daily until disease progression, unacceptable toxicity, or patient preference to withdraw from study.
| Study group | Role | What they receive |
|---|---|---|
| Abemaciclib + LY3214996 | Experimental | Subjects will receive Abemaciclib 150 mg orally twice daily with LY3214996 200 mg orally daily until disease progression, unacceptable toxicity, or patient preference to withdraw from study. Receives: Drug: Abemaciclib; Drug: LY3214996 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
The number of patients who achieve a best overall response of complete response (CR) or partial response (PR) divided by the total number of patients treated (efficacy population) as determined by RECIST v1.1.
Measured: from cycle 1 day 1 until safety follow up visit (up to 1 year)
Secondary outcomes (3)
Number of Patients With Treatment Related Adverse Events Grade 3 or Above
Number of unique patients with any Abemaciclib or LY3214996 treatment related (possible, probable, or definite) adverse events with grade >=3. CTCAE Version 5.0 will be used.
Measured: baseline until safety follow up visit (up to 1 year)
Duration of Overall Response Rate
Measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented through RECIST v1.1. Please note that there were no patients who achieved Complete Response (CR) or Partial Response (PR) within this study.
Measured: up to 1 year
Progression Free Survival
The time from the date of start of treatment to the first date of the observed clinical or radiologically documented PD or death due to any cause, whichever occurs first. For patients who are not known to have died or progressed as of the data-inclusion cut-off date, PFS time will be censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systematic anticancer therapy. Assessment are completed using RECIST v1.1. Kaplan-Meier methods will be used and the median and 95% confidence intervals will be calculated.
Measured: up to 1 year, 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2020
- Study start5 Oct 2020
- Primary completion7 Aug 2023
- Study completion7 Aug 2023
Why it stopped: Lack of efficacy.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CancerStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anita Turk
- Sponsor type
- University, hospital or other
- Collaborators
- Eli Lilly and Company
- Responsible party
- Sponsor-investigator, Anita Turk, Indiana University
- Investigators
- Anita Turk, MD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04534283
- Sponsor's protocol ID
- CTO-IUSCC-0730
- Status last verified
- Aug 2024
- First submitted
- 27 Aug 2020
- Last updated
- 7 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Basket Trial of an ERK1/2 Inhibitor (LY3214996) in Combination With Abemaciclib for Patients Whose Tumors Harbor Pathogenic Alterations in BRAF, RAF1, MEK1/2, ERK1/2, and NF1.
- ClinicalTrials.gov ID
- NCT04534283
- Acronym / sponsor ID
- CTO-IUSCC-0730
- Conditions
- Cancer, Cancer Metastatic, BRAF V600E, MEK1 Gene Mutation, MEK2 Gene Mutation, ERK Mutation
- Keywords
- Point Mutation, Metastatic Cancer, Advanced Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of efficacy.
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Anita TurkUniversity, hospital or other
- Collaborators
- Eli Lilly and Company
- Study start
- 5 Oct 2020 (actual)
- Primary completion
- 7 Aug 2023 (actual)
- Study completion
- 7 Aug 2023 (actual)
- First posted
- 1 Sep 2020 (actual)
- Results
- Posted 7 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of CTO-IUSCC-0730 study is to assess the clinical efficacy of LY3214996 in combination with abemaciclib at the recommended phase 2 dose of LY3214996 200 mg orally daily and abemaciclib 150 mg orally twice daily. Patients will be treated until evidence of disease progression, non-compliance with study protocol, unacceptable major toxicity, at subject's own request for withdrawal, or if the study closes for any reason.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Abemaciclib + LY3214996 | Experimental | Drug: Abemaciclib, Drug: LY3214996Subjects will receive Abemaciclib 150 mg orally twice daily with LY3214996 200 mg orally daily until disease progression, unacceptable toxicity, or patient preference to withdraw from study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Have a histological or cytological diagnosis of advanced unresectable or metastatic cancer (American Joint Committee on Cancer Staging Criteria) (Edge et al. 2009).
- 2. The patient must be, in the judgement of the investigator, an appropriate candidate for experimental therapy, either after available standard therapies (per available local guidelines) have failed to provide clinical benefit for their disease or after the patient has refused standard treatments.
- 3. Have one of the following alterations as defined below using a CLIA-certified next-generation sequencing test:
- Point mutation in BRAF, RAF1, MEK1/2, or ERK1/2 that have been previously characterized to be gain-of-function mutations. These mutations have to be specified as gain-of-function as listed in the OncoKB and/or JAX-CKB databases. i. Patients with NSCLC that harbor BRAF V600E treated with prior RAF and/or MEK inhibition therapy will be excluded.
- Patients with tumor types other than NSCLC that harbor BRAF V600E mutations who have been treated and progressed on prior BRAF and/or MEK inhibition will be included.
Key exclusion criteria (24 listed)
- Have a serious concomitant systemic disorder (for example, active infection or a gastrointestinal disorder causing clinically significant symptoms such as nausea, vomiting or diarrhea, or profound immune suppression) that, in the opinion of the investigator, would compromise the patient's ability to adhere to the protocol.
- Have or known activated/reactivated hepatitis A, B, or C (screening is not required).
- Uncontrolled human immunodeficiency virus (HIV) infection are considered ineligible. HIV- infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- Have symptomatic and untreated central nervous system (CNS) malignancy or metastasis (screening is not required).
- Have current hematologic malignancies, acute or chronic leukemia
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 |
|---|---|---|
| AbemaciclibAlso: LY2835219Subjects will receive Abemaciclib 150 mg orally twice daily until disease progression, unacceptable toxicity, or patient preference to withdraw from study. | Drug | Abemaciclib + LY3214996 |
| LY3214996Subjects will recieve LY3214996 200 mg orally daily until disease progression, unacceptable toxicity, or patient preference to withdraw from study. | Drug | Abemaciclib + LY3214996 |
Primary outcome
Overall Response Rate
Time frame: from cycle 1 day 1 until safety follow up visit (up to 1 year)
The number of patients who achieve a best overall response of complete response (CR) or partial response (PR) divided by the total number of patients treated (efficacy population) as determined by RECIST v1.1.
3 secondary outcomes
Number of Patients With Treatment Related Adverse Events Grade 3 or Above
Time frame: baseline until safety follow up visit (up to 1 year)
Duration of Overall Response Rate
Time frame: up to 1 year
Progression Free Survival
Time frame: up to 1 year, 1 month
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Anita Turk, MD principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Abemaciclib and LY3214996 in people with Cancer and Cancer Metastatic, run by Anita Turk 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 24 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: stopped early, as of the sponsor's last update on 7 Aug 2024. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Overall Response Rate (time frame: from cycle 1 day 1 until safety follow up visit (up to 1 year)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Aug 2024.