Hepatocellular Carcinoma
Conditions
Brief summary
The main purpose of this study is to evaluate the effectiveness of the combination of nivolumab and abemaciclib for the treatment of hepatocellular carcinoma. Other goals of this study are to learn about the side effects that this combination of drugs may cause and to learn more about how these drugs work by studying blood and tissue.
Interventions
DRUGAbemaciclib
Abemaciclib will be given at a dose of 150mg by mouth twice daily continuously for the duration of trial therapy.
DRUGNivolumab
Nivolumab will be administered at a dose of 480mg IV every 28 days. Treatment with nivolumab will begin after an initial 7-day treatment period with abemaciclib monotherapy.
Sponsors
Abramson Cancer Center at Penn Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects must have hepatocellular carcinoma (HCC) that is inoperable (where surgery is not indicated due to disease extent, co-morbidities, or other technical reasons) 2. Histologic confirmation of HCC is not required for screening but is required prior to initiation of study treatment. Subjects with hepatocholangiocarcinoma or cholangiocarcinoma are not eligible. 3. Tumor must be positive for retinoblastoma (RB) expression by immunohistochemistry 4. Age \> 18 years and ability to understand and the willingness to sign a written informed consent document. 5. ECOG performance status of 0 or 1 6. Childs-Pugh score of \<7 7. Life expectancy of at least 12 weeks 8. Must be able to swallow tablets 9. Must be willing to comply with protocol procedures (including completion of diaries and outcome measures) 10. Local or loco-regional therapy to the liver (i.e. surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed \> 4 weeks prior to enrollment 11. Must be willing to undergo a pretreatment and on-treatment biopsy and have a tumor site that is accessible for core needle biopsy 12. Measurable or evaluable disease as defined by RECIST v. 1.1 13. Women of childbearing potential must have a negative serum pregnancy test performed within 7 days of the first dose of abemaciclib (see Appendix A for definition of childbearing potential). Female subjects of childbearing potential must use an approved contraceptive method (detailed in Appendix A) for the duration of the study and an additional 3 weeks after the final dose of abemaciclib. 14. Subjects with hepatitis B must have an HBV viral load \< 100 IU/mL by PCR during screening 15. Must have adequate organ and hematopoietic function as defined below:
Exclusion criteria
1. Any history of a serious medical or psychiatric condition that would prevent the subject from signing the informed consent form 2. Pregnant or breastfeeding 3. Use of any chemotherapy within 3 weeks prior to the first study treatment date 4. Use of any experimental therapy within 4 weeks or 5 half-lives, whichever is longer, prior to the first study treatment date 5. Use of radiation within 2 weeks prior to the first study treatment date (4 weeks if radiation to liver as per section 4.1) 6. Prior treatment with a CDK 4/6 inhibitor 7. Prior treatment with a PD-1 or PD-L1 inhibitor 8. Those who have not recovered from adverse events \< Grade 1 from prior therapy, with the exceptions of alopecia of any grade or stable peripheral neuropathy \< Grade 2 9. Subjects may not receive concomitant anticancer agents or radiation. Antiviral agents aimed at treating infectious hepatitis are permitted 10. History of or suspected hypersensitivity to nivolumab or abemaciclib 11. Uncontrolled ascites 12. Esophageal varices requiring treatment within the past 6 months (banding or medication) 13. Subjects with uncontrolled brain metastases. Subjects with brain metastases must have stable neurological status following local therapy (surgery or radiation) for at least 4 weeks prior to first study treatment and must be off of steroids related to the brain metastases. 14. Any concurrent condition requiring the continued or anticipated use of systemic steroids beyond physiologic replacement dosing (excluding non-systemic inhaled, topical skin, nasal, and/or ophthalmic corticosteroids). All other systemic corticosteroids above physiologic replacement dosing must be discontinued at least 4 weeks prior to first study treatment 15. Active drug or alcohol use or dependence as documented in the chart that, in the opinion of the investigator, would interfere with adherence to study requirements 16. Active bacterial or fungal infection requiring IV therapy at the start of protocol treatment 17. A second primary malignancy that, in the judgment of the investigator, may affect the interpretation of results 18. Any illness or condition that in the opinion of the investigator may affect the safety of the subject or the evaluation of any study endpoint (e.g. interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, 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) 19. Personal history of ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest 20. Prior organ allograft or allogeneic bone marrow transplantation 21. Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication 22. Active autoimmune disease, except for vitiligo, type 1 diabetes mellitus, asthma, atopic dermatitis, or endocrinopathies manageable by hormone replacement; other autoimmune conditions may be allowable at the discretion of the Principal Investigator 23. Any other conditions judged by the investigator that would limit the evaluation of the subject 24. HIV positive by PCR
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | up to 2 years | The objective response rate is determined by the percentage of participants on study attaining a partial or complete response as noted per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | From the start of study treatment until disease progression, death, whichever came first up to 2 years | Progression-Free survival is determined from the start of study treatment until the time of documented disease progression or death per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and iRECIST criteria (guidelines for response criteria for use in trials testing immunotherapies) |
| Duration of Response | up to 2 years | Time from the first recorded partial response or complete response (whichever comes first) defined Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; until disease progression or death |
| Overall Survival | From the start of treatment to death, due to any cause or last patient contact alive, assessed up to 2 years | — |
Countries
United States
Participant flow
Pre-assignment details
7 met inclusion criteria and began treatment.
Participants by arm
| Arm | Count |
|---|---|
| Abemaciclib & Nivolumab Subjects will receive abemaciclib monotherapy 150mg twice daily for seven days then will initiate nivolumab 480mg IV every 28 days while continuing twice daily abemaciclib.
Abemaciclib: Abemaciclib will be given at a dose of 150mg by mouth twice daily continuously for the duration of trial therapy.
Nivolumab: Nivolumab will be administered at a dose of 480mg IV every 28 days. Treatment with nivolumab will begin after an initial 7-day treatment period with abemaciclib monotherapy. | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Abemaciclib & Nivolumab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 7 |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 3 / 7 |
Outcome results
Primary
Objective Response Rate
The objective response rate is determined by the percentage of participants on study attaining a partial or complete response as noted per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Abemaciclib & Nivolumab | Objective Response Rate | 1 Participants |
Secondary
Duration of Response
Time from the first recorded partial response or complete response (whichever comes first) defined Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; until disease progression or death
Time frame: up to 2 years
Population: Subjects with objective response
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Abemaciclib & Nivolumab | Duration of Response | 10.2 months |
Secondary
Overall Survival
Time frame: From the start of treatment to death, due to any cause or last patient contact alive, assessed up to 2 years
Population: All subjects who received study therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abemaciclib & Nivolumab | Overall Survival | 7.9 months |
Secondary
Progression-Free Survival
Progression-Free survival is determined from the start of study treatment until the time of documented disease progression or death per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and iRECIST criteria (guidelines for response criteria for use in trials testing immunotherapies)
Time frame: From the start of study treatment until disease progression, death, whichever came first up to 2 years
Population: All subjects who received study therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Abemaciclib & Nivolumab | Progression-Free Survival | 2.1 months |