A Basket Trial of an ERK1/2 Inhibitor (LY3214996) in Combination With Abemaciclib.

NCT04534283 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: CTO-IUSCC-0730
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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. 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; RAF1 Gene Mutation

Keywords

Point Mutation; Metastatic Cancer; Advanced Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  baseline until safety follow up visit (up to 1 year)

• Duration of Overall Response Rate

  up to 1 year

• Progression Free Survival

  up to 1 year, 1 month

Study Arms (1)

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.

Drug: Abemaciclib; Drug: LY3214996

Interventions

Abemaciclib DRUG

Subjects will receive Abemaciclib 150 mg orally twice daily until disease progression, unacceptable toxicity, or patient preference to withdraw from study.

Also known as: LY2835219

Abemaciclib + LY3214996

LY3214996 DRUG

Subjects will recieve LY3214996 200 mg orally daily until disease progression, unacceptable toxicity, or patient preference to withdraw from study.

Abemaciclib + LY3214996

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a histological or cytological diagnosis of advanced unresectable or metastatic cancer (American Joint Committee on Cancer Staging Criteria) (Edge et al. 2009).
• \. 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.
• \. Have one of the following alterations as defined below using a CLIA-certified next-generation sequencing test:
• a. 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.
• ii. 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.
• iii. Patients with NSCLC that harbor BRAF V600E will only be enrolled if they are not a candidate for FDA approved therapy
• 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.
• \. Have measurable disease amenable to biopsy. If biopsy is deemed unsafe at time of procedure, patients will remain eligible for study.
• \. Must be able to provide written informed consent and HIPAA authorization for release of personal health information.
• \. 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.
• \. 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.
• \. 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
• \. Are at least 18 years old at the time of screening.

You may not qualify if:

• 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
• 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).
• a. 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.

Sponsors & Collaborators

• Anita Turk: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

Indiana University Hospital / IU Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis

Interventions

abemaciclib; LY3214996

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Early termination leading to smaller number of patients enrolled than planned.

Results Point of Contact

• Title: Dr. Anita Turk
• Organization: IndianaU

aaturk@iu.edu

(317) 274-0335

Study Officials

• Anita Turk, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Clinical Medicine

Study Record Dates

• First Submitted: August 27, 2020
• First Posted: September 1, 2020
• Study Start: October 5, 2020
• Primary Completion: August 7, 2023
• Study Completion: August 7, 2023
• Last Updated: August 7, 2024
• Results First Posted: August 7, 2024

Record last verified: 2024-08

Locations

US (1)