ABEMA Alone or in COMBO With MK-6482

NCT04627064 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 20-2845P50CA101942-20
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This research study will assess whether abemaciclib alone or in combination with MK-6482 are safe and effective in slowing down the growth of clear cell renal cell carcinoma (ccRCC). The names of the study drugs in this investigational combination are:

• Abemaciclib
• MK-6482

Conditions

Clear Cell Renal Cell Carcinoma

Keywords

Clear Cell Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (3)

• Objective Response Rate (ORR) in Abemaciclib Arm (Arm 1)

  ORR is defined as percentage of patients with partial (PR) or complete response (CR) as best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by central review. Imaging assessments will be performed every 8 weeks during the first six months of the study, then every 12 weeks thereafter.

  From the start of protocol treatment until disease progression or deaths. The total duration assessed was up to 3 months, as all patients either progressed, died, or withdrew from the study within that timeframe.

• Objective Response Rate (ORR) in Abemaciclib and MK-6482 Arm (Arm 2)

  Percentage of patients with partial (PR) or complete response (CR) as best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by central review. Imaging assessments will be performed every 8 weeks during the first six months of the study, then every 12 weeks thereafter.

  From the start of protocol treatment until disease progression or death

• Maximum Tolerated Dose (MTD) in Abemaciclib and MK-6482 (Arm 2)

  MTD of abemaciclib plus MK-6482, defined as the highest dose studied at which no more than 1 of 6 subjects has experienced a dose limiting toxicity (DLT) in cycle 1.

  Cycle 1 of during the combination therapy (Arm 2)

Secondary Outcomes (7)

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE 5 of Abemaciclib and MK-6482 (Arm 2)

  From start of protocol treatment until 90 days after treatment discontinuation, or until initiation of new cancer-directed treatment, or until death, whichever occurs first.

• Duration of Response (DOR) in Patients Who Achieve an Objective Response in Abemaciclib Arm (Arm 1)

  From start of complete response or partial response (whichever is first recorded) until the date of disease progression or death.

• Progression-free Survival (PFS) in Abemaciclib Arm (Arm 1)

  From trial treatment start to the earlier of progression or death due to any cause. The total duration assessed was up to 3 months, as all patients either progressed, died, or withdrew from the study within that timeframe.

• Overall Survival (OS) in Abemaciclib Arm (Arm 1)

  From trial treatment start to death due to any cause or date last known alive, up to 23 months

• Duration of Response (DOR) in Patients Who Achieve an Objective Response in Abemaciclib and MK-6482 Arm (Arm 2)

  From the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the date of disease progression or death due to any cause.

Study Arms (2)

Abemaciclib-Arm 1

EXPERIMENTAL

Arm 1 * Abemaciclib will be taken at a standard recommended starting dose 2X daily during 28 day study cycles and will be taken until radiographic progression, unacceptable toxicity or withdrawal. * Imaging assessments will be performed every 8 weeks during the first six months of the study, then every 12 weeks, in both Arm 1 and Arm 2.

Drug: Abemaciclib

Abemaciclib and MK-6482-Arm 2

EXPERIMENTAL

Arm 2 * Arm 2 will start enrolling only after there is experience with Arm 1 to see what abemaciclib effects are when given alone, * Dose escalation will occur following a 3+3 design. * Abemaciclib will be taken 2X daily uring 28 day study cycle * MK-6482 will be taken 1x daily during 28 day study cycle * Imaging assessments will be performed every 8 weeks during the first six months of the study, then every 12 weeks, in both arms.

Drug: Abemaciclib; Drug: MK-6482

Interventions

Abemaciclib DRUG

Tablet taken orally

Also known as: Verzenio

Abemaciclib and MK-6482-Arm 2; Abemaciclib-Arm 1

MK-6482 DRUG

Tablet taken orally

Also known as: HIF-2α inhibitor

Abemaciclib and MK-6482-Arm 2

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed unresectable advanced or metastatic renal cell carcinoma with clear cell component. Patients with extensive sarcomatoid histology are accepted.
• Participants must have failed or developed an intolerance to at least 1 prior anti-VEGFR systemic therapy and 1 immune checkpoint inhibitor for metastatic RCC. No limit on the number of prior lines of therapies.
• Measurable disease as per RECIST 1.1. See section 12 for the evaluation of measurable disease.
• Age ≥ 18 years
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
• Participants must undergo fresh tumor biopsy unless medically unsafe or not feasible.
• Normal organ and marrow function as defined below:
• Absolute neutrophil count ≥1,500/mcL
• Platelets ≥100,000/mcL
• Hemoglobin ≥10g/dL (transfusions allowed)
• Total bilirubin ≤2.0 x institutional upper limit of normal with the following exception: patients with known Gilbert disease should have a serum bilirubin ≤ 3 x ULN
• AST(SGOT)/ALT(SGPT)≤3.0 × institutional upper limit of normal with the following exception: patients with known liver metastases should have AST and ALT
• ≤ 5 x ULN
• Creatinine clearance ≥30 mL/min/1.73 m2 according to the Cockcroft-Gault equation. (APPENDIX F)
• Urine protein/creatinine ratio (UPC ratio) ≤2

You may not qualify if:

• A patient will be excluded from the study if he or she meets any of the following criteria:
• Patients receiving any other investigational agents.
• Patients who received prior CDK4/6 inhibitors.
• For Arm 2 only, patients who have received prior HIF-2α inhibitor.
• Participants who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) ≤ 4 effective half-lives prior to starting study drug or who have not recovered from side effects of such therapy to grade 1 or less (except for non-clinically significant laboratory abnormalities).
• Patients must have discontinued all biologic therapy including therapeutic antibodies at least 28 days before C1D1.
• Participants who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy to at least grade 1.
• O2 saturation \<92% by arterial blood gas analysis or pulse oximetry on room air
• Untreated deep vein thrombosis or pulmonary embolism, or event of deep vein thrombosis or pulmonary embolism within 2 weeks of treatment start. Patient should be on at least 1 week of anticoagulation before C1D1.
• The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea)."
• Patient with active systemic bacterial infection (requiring IV antibiotics at the time of initiating study treatment), fungal infection, or detectable viral infection. Patients with known viral infection (such as HIV) are excluded given the potential for interactions between antiretroviral agents and abemaciclib, and the potential for increased risk of lifethreatening infection with therapy that is myelosuppressive. If you are not known to have HIV, a HIV test is required.
• Patients with known Hepatitis B or Hepatitis C infection are excluded only if there is evidence of active infection (detectable Hepatitis B surface antigen, detectable Hepatitis C RNA).
• Prior allogenic stem cell or solid organ transplant.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Participants who have undergone major surgery ≤ 4 weeks (28 days) prior to starting study drug(s) or who have not recovered from side effects of such therapy.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Eli Lilly and Company: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• Meiman D, Skaar TC, Shugg T, Quinney SK. Physiologically Based Pharmacokinetic Model to Assess the Drug-Drug-Gene Interaction Potential of Belzutifan in Combination With Cyclin-Dependent Kinase 4/6 Inhibitors. JCO Precis Oncol. 2025 Jul;9:e2500153. doi: 10.1200/PO-25-00153. Epub 2025 Jul 25.

  PMID: 40712111 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

abemaciclib; belzutifan

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Toni Choueiri, M.D
• Organization: Dana-Farber Cancer Institute

toni_choueiri@dfci.harvard.edu

617-6325456

Study Officials

• Toni K Choueiri, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 9, 2020
• First Posted: November 13, 2020
• Study Start: December 31, 2020
• Primary Completion: February 9, 2024
• Study Completion: August 4, 2024
• Last Updated: July 25, 2025
• Results First Posted: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (1)