Abemaciclib + Nivolumab in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma That Progressed or Recurred Within Six Months After Platinum-based Chemotherapy

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03655444
• Collaborator: Eli Lilly and Company (Industry)
• Enrollment: 6
• Location: 1
• Arms: 2
• Actual Duration (Months): 14.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

In phase I of the trial, the investigators aim to explore the safety and feasibility of abemaciclib in combination with nivolumab in patients with recurrent/metatstatic head and neck squamous cell carcinoma (RM-HNSCC). A dose de-escalation study design will be used to determine the recommended phase II dose (RP2D) of abemaciclib given with the standard dose of nivolumab.

In phase II of the trial, the investigators aim to determine if abemaciclib and nivolumab will improve the one year survival from 36% (historical comparison with nivolumab) to 60% (abemaciclib + nivolumab) in patients with RM-HNSCC that had progressed or recurred within six months after platinum-based chemotherapy. Patients will be treated with abemaciclib at the recommended phase 2 dose (RP2D) in combination with standard doses of nivolumab. If this aim is met, genome sequencing, bulk and single cell RNAseq, and selected protein expression and deep cellular phenotyping will be performed on tumor tissue and blood obtained before and during treatment with abemaciclib and nivolumab. These biomarker data will be correlated with survival and tumor response to abemaciclib and nivolumab.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Squamous Cell Carcinoma	Drug: Abemaciclib; Drug: Nivolumab; Procedure: Tumor biopsy; Procedure: Peripheral blood; Other: EORTC QLQ-30	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective Phase I and II Trial of Abemaciclib + Nivolumab in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma That Progressed or Recurred Within Six Months After Platinum-based Chemotherapy
• Actual Study Start Date: May 29, 2019
• Actual Primary Completion Date: Aug 24, 2020
• Actual Study Completion Date: Aug 24, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase I: Abemaciclib + Nivolumab Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.	Drug: Abemaciclib; Abemaciclib is an investigational agent for this trial and will be supplied by Lilly Oncology, free of charge to the patient.; Other Names: Verzenio ; Drug: Nivolumab; Nivolumab is commercially available; Other Names: Opdivo
Experimental: Phase II: Abemaciclib + Nivolumab Phase II Lead-in: Patients will be treated with abemaciclib monotherapy at the recommended phase II dose (150 mg) on Day -7 through Day -1 prior to starting Cycle 1 with the combination of abemaciclib and nivolumab. Patients will proceed directly from Day -1 to Cycle 1 Day 1 of combination abemaciclib + nivolumab, there is not a Day 0. Patients will be treated with abemaciclib at the RP2D (150 mg) (Days 1 through 28) + nivolumab (480 mg, Day 1) of each 4-week cycle.	Drug: Abemaciclib; Abemaciclib is an investigational agent for this trial and will be supplied by Lilly Oncology, free of charge to the patient.; Other Names: Verzenio ; Drug: Nivolumab; Nivolumab is commercially available; Other Names: Opdivo ; Procedure: Tumor biopsy; Phase II patients only If the patient consents, fresh tumor tissue will be collected at baseline and then during Cycle 2 (between days 8-22) of abemaciclib and nivolumab.; Procedure: Peripheral blood; Phase II patients only Peripheral blood will be collected at baseline, at the end of the Lead In (cycle 1 day 1 prior to treatment), during cycle 2 (between days 8-22), and during cycle 3 (between days 21-28). If patient does not have progression after cycle 3, patient will also have peripheral blood collected at time of progression.; Other: EORTC QLQ-30; Phase II patients only Screening , Cycle 2 D1, Cycle 4 D1, and End of treatment (EOT)

Outcome Measures

Primary Outcome Measures

1. Phase I Only: Determine the Recommended Phase 2 Dose of Abemaciclib Combined With a Fixed Dose of Nivolumab [Completion of enrollment to Phase I portion of study (estimated to be 3 months)]

   -The RP2D of abemaciclib is defined as the highest dose level at which fewer than 2 patients of a cohort of three patients experience a dose-limiting toxicity (DLT) during the first cycle.

2. Overall Survival (OS) Rate [Until death (estimated average of 13 months)]

   OS is defined as the time from the date of treatment to the date of death, censored at the last follow-up otherwise. The mean survival time and standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.

Secondary Outcome Measures

1. Phase II Only: Best Overall Tumor Response [Through completion of treatment (estimated to be 5 months)]

   Complete response: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, Disappearance of all non-target lesions and normalization of tumor marker level. Partial response: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.

2. Phase II Only: Duration of Tumor Response [Through completion of treatment (estimated to be 5 months)]

   -The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

3. Progression-free Survival (PFS) [Through completion of treatment (estimated to be 5 months)]

   -PFS is defined as the time from treatment to the date of progression or death, whichever occurs first. The alive patients without progression is censored at the last follow-up.

4. Adverse Events (AEs) Associated With the Combination of Abemaciclib and Nivolumab. [Through 30 days after completion of treatment (estimated to be 6 months)]

   -The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.

5. Phase II Lead-In Only: Changes in Peripheral Blood Lymphocyte Subsets [Compare before and after one week of abemaciclib monotherapy]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Incurable RM-HNSCC, defined as disease not amenable to cure by surgery and/or radiation therapy (or patient declines or is ineligible for surgery and/or radiation therapy).

• Disease Evaluation:

• Phase I: evaluable or measurable disease.

• Phase II: measurable disease, defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by chest x-ray, or ≥ 10 mm by clinical exam.

• Prior Treatment:

• Phase I: any number of lines of prior therapy for RM-HNSCC.

• Phase I: prior therapy with inhibitors of CDK4/6 or PD-L1/PD-1 is acceptable.

• Phase II: RM-HNSCC that progressed or recurred within six months of platinum-based therapy (given for curable or incurable disease).

• Phase II: prior therapy with inhibitors of CDK4/6 or PD-L1/PD-1 is not acceptable.

• 18 years of age or older

• Performance status 0-1 (ECOG)

• Adequate blood and organ function as defined:

• Absolute neutrophil count ≥ 1,500/mcL

• Platelets ≥ 100,000/mcL

• Hemoglobin ≥ 8.0 g/dL

• Total bilirubin ≤ 1.5 x ULN mg/dL

• AST(SGOT) ≤ 3 x IULN and ALT(SGPT) ≤ 3 x IULN

• Creatinine ≤ 2 x ULN OR creatinine clearance ≥ 40 mL/min/1.73 m2

• INR ≤ 1.5 x ULN and PTT ≤ 1.5 x ULN (Patients are allowed to be on anticoagulation)

• Able to swallow oral medication

• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) beginning 14 days prior to first dose of abemaciclib, through the dosing period, and for at least 28 days after.

• Signed IRB approved written informed consent document.

Exclusion Criteria:

• Phase II: prior inhibitors of CDK4/6 or PD-L1/PD-1 for treatment of incurable HNSCC.

• Radiation within 14 days of treatment start (patients who received radiotherapy must have completed and fully recovered from the acute side effects of radiotherapy), chemotherapy, targeted or investigational therapy within 21 days of treatment start.

• History of other malignancy ≤ 1 year prior to consent with the exception of completely resected skin carcinoma or other cancers with a low risk of recurrence.

• Ongoing toxicity attributed to prior anti-cancer therapy that is > grade 1, except alopecia or peripheral neuropathy

• Active central nervous system metastases: defined as currently receiving radiation therapy to metastatic CNS disease. Once radiation therapy is completed, patients with CNS disease are eligible if they meet all other criteria for enrollment.

• History of severe allergic reactions attributed to agents used in the study.

• Serious uncontrolled inter-current illness within the 3 months prior to study entry or psychiatric illness/social situations that would limit compliance with study requirements.

• Serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (i.e., 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).

• Active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C [for example, hepatitis B surface antigen positive]. Screening is not required for enrollment.

• History of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.

• Pregnant and/or breastfeeding. Patient must have a negative serum pregnancy test within 7 days of first dose of treatment.

• Active serious autoimmune disease requiring systemic immunosuppression (biologics, prednisone equivalent dose > 20 mg/day).

• Current use of strong CYP3A inhibitors or inducers.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine
• Eli Lilly and Company

Investigators

• Principal Investigator: Douglas R Adkins, M.D., Washington University School of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 10, 2019

More Information

Additional Information:

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Publications

None provided.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT03655444
• Other Study ID Numbers: 201810019
• First Posted: Aug 31, 2018
• Last Update Posted: Dec 3, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Nivolumab

Study Results

Participant Flow

Arm/Group Title	Phase I: Abemaciclib + Nivolumab	Phase II: Abemaciclib + Nivolumab
Arm/Group Description	Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.	Phase II Lead-in: Patients will be treated with abemaciclib monotherapy at the recommended phase II dose on Day -7 through Day -1 prior to starting Cycle 1 with the combination of abemaciclib and nivolumab. Patients will proceed directly from Day -1 to Cycle 1 Day 1 of combination abemaciclib + nivolumab, there is not a Day 0. Patients will be treated with abemaciclib at the RP2D (Days 1 through 28) + nivolumab (480 mg, Day 1) of each 4-week cycle.
Period Title: Overall Study
STARTED	3	3
COMPLETED	3	3
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Phase I: Abemaciclib + Nivolumab	Phase II: Abemaciclib + Nivolumab	Total
Arm/Group Description	Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.	Phase II Lead-in: Patients will be treated with abemaciclib monotherapy at the recommended phase II dose on Day -7 through Day -1 prior to starting Cycle 1 with the combination of abemaciclib and nivolumab. Patients will proceed directly from Day -1 to Cycle 1 Day 1 of combination abemaciclib + nivolumab, there is not a Day 0. Patients will be treated with abemaciclib at the RP2D (Days 1 through 28) + nivolumab (480 mg, Day 1) of each 4-week cycle.	Total of all reporting groups
Overall Participants	3	3	6
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62	62	62
Sex: Female, Male (Count of Participants)
Female	1 33.3%	0 0%	1 16.7%
Male	2 66.7%	3 100%	5 83.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	3 100%	3 100%	6 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 66.7%	2 66.7%	4 66.7%
White	1 33.3%	1 33.3%	2 33.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	3 100%	3 100%	6 100%

Outcome Measures

1. Primary Outcome

Title	Phase I Only: Determine the Recommended Phase 2 Dose of Abemaciclib Combined With a Fixed Dose of Nivolumab
Description	-The RP2D of abemaciclib is defined as the highest dose level at which fewer than 2 patients of a cohort of three patients experience a dose-limiting toxicity (DLT) during the first cycle.
Time Frame	Completion of enrollment to Phase I portion of study (estimated to be 3 months)

Outcome Measure Data

Analysis Population Description

Only phase I participants were evaluable for this outcome measure.

Arm/Group Title	Phase I: Abemaciclib + Nivolumab	Phase II: Abemaciclib + Nivolumab
Arm/Group Description	Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.	Phase II Lead-in: Patients will be treated with abemaciclib monotherapy at the recommended phase II dose on Day -7 through Day -1 prior to starting Cycle 1 with the combination of abemaciclib and nivolumab. Patients will proceed directly from Day -1 to Cycle 1 Day 1 of combination abemaciclib + nivolumab, there is not a Day 0. Patients will be treated with abemaciclib at the RP2D (Days 1 through 28) + nivolumab (480 mg, Day 1) of each 4-week cycle.
Measure Participants	3	0
Number [mg twice per day]	150

2. Primary Outcome

Title	Overall Survival (OS) Rate
Description	OS is defined as the time from the date of treatment to the date of death, censored at the last follow-up otherwise. The mean survival time and standard error were underestimated because the largest observation was censored and the estimation was restricted to the largest event time.
Time Frame	Until death (estimated average of 13 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I and Phase II: Abemaciclib + Nivolumab
Arm/Group Description	Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.
Measure Participants	6
Mean (Standard Error) [months]	3.689 (0.7281)

3. Secondary Outcome

Title	Phase II Only: Best Overall Tumor Response
Description	Complete response: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, Disappearance of all non-target lesions and normalization of tumor marker level. Partial response: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria.
Time Frame	Through completion of treatment (estimated to be 5 months)

Outcome Measure Data

Analysis Population Description

-Phase II patients are the only patients evaluable.

Arm/Group Title	Phase I: Abemaciclib + Nivolumab	Phase II: Abemaciclib + Nivolumab
Arm/Group Description	Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.	Phase II Lead-in: Patients will be treated with abemaciclib monotherapy at the recommended phase II dose on Day -7 through Day -1 prior to starting Cycle 1 with the combination of abemaciclib and nivolumab. Patients will proceed directly from Day -1 to Cycle 1 Day 1 of combination abemaciclib + nivolumab, there is not a Day 0. Patients will be treated with abemaciclib at the RP2D (Days 1 through 28) + nivolumab (480 mg, Day 1) of each 4-week cycle.
Measure Participants	0	3
Count of Participants [Participants]	1 33.3%

4. Secondary Outcome

Title	Phase II Only: Duration of Tumor Response
Description	-The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Time Frame	Through completion of treatment (estimated to be 5 months)

Outcome Measure Data

Analysis Population Description

Data was not collected for this outcome measure.

Arm/Group Title	Phase I: Abemaciclib + Nivolumab	Phase II: Abemaciclib + Nivolumab
Arm/Group Description	Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.	Phase II Lead-in: Patients will be treated with abemaciclib monotherapy at the recommended phase II dose on Day -7 through Day -1 prior to starting Cycle 1 with the combination of abemaciclib and nivolumab. Patients will proceed directly from Day -1 to Cycle 1 Day 1 of combination abemaciclib + nivolumab, there is not a Day 0. Patients will be treated with abemaciclib at the RP2D (Days 1 through 28) + nivolumab (480 mg, Day 1) of each 4-week cycle.
Measure Participants	0	0

5. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	-PFS is defined as the time from treatment to the date of progression or death, whichever occurs first. The alive patients without progression is censored at the last follow-up.
Time Frame	Through completion of treatment (estimated to be 5 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I and Phase II: Abemaciclib + Nivolumab
Arm/Group Description	Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.
Measure Participants	6
Mean (Standard Error) [months]	2.82258 (0.64434)

6. Secondary Outcome

Title	Adverse Events (AEs) Associated With the Combination of Abemaciclib and Nivolumab.
Description	-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting.
Time Frame	Through 30 days after completion of treatment (estimated to be 6 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I and Phase II: Abemaciclib + Nivolumab
Arm/Group Description	Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.
Measure Participants	6
Anemia	5 166.7%
Hyperthyroidism	1 33.3%
Hypothyroidism	1 33.3%
Constipation	2 66.7%
Diarrhea	3 100%
Dry mouth	1 33.3%
Dysphagia	3 100%
Mucositis oral	1 33.3%
Nausea	4 133.3%
Vomiting	3 100%
Chills	1 33.3%
Edema face	1 33.3%
Fatigue	5 166.7%
Non-cardiac chest pain	1 33.3%
Lung infection	2 66.7%
Thrush	2 66.7%
Vaginal infection	1 33.3%
Alanine aminotransferase increased	1 33.3%
Alkaline phosphatase increased	2 66.7%
Aspartate aminotransferase increased	3 100%
Blood bilirubin increased	1 33.3%
Cholesterol high	1 33.3%
Creatinine increased	6 200%
Blood bicarbonate decreased	1 33.3%
Lymphocyte count decreased	6 200%
Neutrophil count decreased	2 66.7%
Platelet count decreased	2 66.7%
Weight loss	4 133.3%
White blood cell decreased	2 66.7%
Anorexia	3 100%
Dehydration	1 33.3%
Hypercalcemia	2 66.7%
Hyperglycemia	4 133.3%
Hyperkalemia	2 66.7%
Hypoalbuminemia	3 100%
Hypocalcemia	1 33.3%
Hypoglycemia	1 33.3%
Hypokalemia	2 66.7%
Hypomagnesemia	1 33.3%
Hyponatremia	3 100%
Generalized muscle weakness	1 33.3%
Arthritis	1 33.3%
Chest wall pain	1 33.3%
Dizziness	2 66.7%
Dysarthria	2 66.7%
Headache	1 33.3%
Confusion	1 33.3%
Depression	1 33.3%
Acute kidney injury	1 33.3%
Hematuria	1 33.3%
Aspiration	2 66.7%
Cough	4 133.3%
Nasal congestion	1 33.3%
Respiratory failure	1 33.3%
Sore throat	1 33.3%
Pruritus	2 66.7%
Hypertension	3 100%
Thromboembolic event	1 33.3%

7. Secondary Outcome

Title	Phase II Lead-In Only: Changes in Peripheral Blood Lymphocyte Subsets
Time Frame	Compare before and after one week of abemaciclib monotherapy

Outcome Measure Data

Analysis Population Description

The data was not collected for this outcome measure.

Arm/Group Title	Phase I: Abemaciclib + Nivolumab	Phase II: Abemaciclib + Nivolumab
Arm/Group Description	Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.	Phase II Lead-in: Patients will be treated with abemaciclib monotherapy at the recommended phase II dose on Day -7 through Day -1 prior to starting Cycle 1 with the combination of abemaciclib and nivolumab. Patients will proceed directly from Day -1 to Cycle 1 Day 1 of combination abemaciclib + nivolumab, there is not a Day 0. Patients will be treated with abemaciclib at the RP2D (Days 1 through 28) + nivolumab (480 mg, Day 1) of each 4-week cycle.
Measure Participants	0	0

Adverse Events

Time Frame	Adverse events were collected from start of treatment until 28 days after completion of treatment (median follow-up was 2.8 months)
Arm/Group Title	Phase I and Phase II: Abemaciclib + Nivolumab
Arm/Group Description	Abemaciclib (150 mg) will be administered orally twice per day (with or without food) on Days 1 through 28 of every 4-week cycle Nivolumab 480 mg will be given intravenously (IV) over 30 minutes on Day 1 of every 4-week cycle.
All Cause Mortality
	Phase I and Phase II: Abemaciclib + Nivolumab
	Affected / at Risk (%)	# Events
Total	3/6 (50%)
Serious Adverse Events
	Phase I and Phase II: Abemaciclib + Nivolumab
	Affected / at Risk (%)	# Events
Total	3/6 (50%)
Gastrointestinal disorders
Dysphagia	1/6 (16.7%)
General disorders
Non cardiac chest pain	1/6 (16.7%)
Infections and infestations
Lung infection	2/6 (33.3%)
Investigations
Aspartate aminotransferase increased	1/6 (16.7%)
Renal and urinary disorders
Acute kidney injury	1/6 (16.7%)
Other (Not Including Serious) Adverse Events
	Phase I and Phase II: Abemaciclib + Nivolumab
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Blood and lymphatic system disorders
Anemia	5/6 (83.3%)
Endocrine disorders
Hyperthyroidism	1/6 (16.7%)
Hypothyroidism	1/6 (16.7%)
Gastrointestinal disorders
Constipation	2/6 (33.3%)
Diarrhea	3/6 (50%)
Dry mouth	1/6 (16.7%)
Dysphagia	2/6 (33.3%)
Mucositis oral	1/6 (16.7%)
Nausea	4/6 (66.7%)
Vomiting	3/6 (50%)
General disorders
Chills	1/6 (16.7%)
Edema face	1/6 (16.7%)
Fatigue	5/6 (83.3%)
Infections and infestations
Thrush	2/6 (33.3%)
Vaginal infection	2/6 (33.3%)
Investigations
Alanine aminotransferase increased	1/6 (16.7%)
Alkaline phosphatase increased	2/6 (33.3%)
Aspartate aminotransferase increased	2/6 (33.3%)
Blood bilirubin increased	1/6 (16.7%)
Cholesterol high	1/6 (16.7%)
Creatinine increased	6/6 (100%)
Blood bicarbonate decreased	1/6 (16.7%)
Lymphocyte count decreased	6/6 (100%)
Neutrophil count decreased	2/6 (33.3%)
Platelet count decreased	2/6 (33.3%)
Weight loss	4/6 (66.7%)
White blood cell decreased	2/6 (33.3%)
Hypercalcemia	2/6 (33.3%)
Metabolism and nutrition disorders
Anorexia	3/6 (50%)
Dehydration	1/6 (16.7%)
Hyperglycemia	4/6 (66.7%)
Hyperkalemia	2/6 (33.3%)
Hypoalbuminemia	3/6 (50%)
Hypocalcemia	1/6 (16.7%)
Hypoglycemia	1/6 (16.7%)
Hypokalemia	2/6 (33.3%)
Hypomagnesemia	1/6 (16.7%)
Hyponatremia	3/6 (50%)
Generalized muscle weakness	1/6 (16.7%)
Musculoskeletal and connective tissue disorders
Arthritis	1/6 (16.7%)
Chest wall pain	1/6 (16.7%)
Nervous system disorders
Dizziness	2/6 (33.3%)
Dysarthria	2/6 (33.3%)
Headache	1/6 (16.7%)
Psychiatric disorders
Confusion	1/6 (16.7%)
Depression	1/6 (16.7%)
Renal and urinary disorders
Hematuria	1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
Aspiration	2/6 (33.3%)
Cough	4/6 (66.7%)
Nasal congestion	1/6 (16.7%)
Respiratory failure	1/6 (16.7%)
Sore throat	1/6 (16.7%)
Skin and subcutaneous tissue disorders
Pruritus	2/6 (33.3%)
Vascular disorders
Hypertension	3/6 (50%)
Thromboembolic event	1/6 (16.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.