Abemaciclib With or Without Atezolizumab for mCRPC

NCT04751929 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 20-701
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is testing whether a molecularly targeted chemotherapy drug called abemaciclib and an immunotherapy drug called atezolizumab, alone or in combination, are effective in shrinking or preventing the growth of metastatic prostate cancer. The trial is also testing the safety of the combination of abemaciclib with atezolizumab.

Conditions

Prostate Cancer; Metastatic Castration-resistant Prostate Cancer

Keywords

Prostate Cancer; Metastatic Castration-resistant Prostate Cancer; Abemaciclib; Atezolizumab; CDK4/6; Immunotherapy; PD-L1

Outcome Measures

Primary Outcomes (3)

• 6-month Progression Free Survival (PFS) Rate

  The percentage of participants alive and progression-free at 6 months, as assessed by RECIST 1.1 and PCWG3.

  6 months

• Objective Response Rate (ORR)

  The percentage of evaluable patients who had radiographic response (complete response or partial response) by RECIST 1.1 criteria OR 50% decline in PSA from pretreatment baseline per PCWG3 criteria.

  6 months

• Number of Participants Experiencing Dose Limiting Toxicity (DLT) in Biomarker-Unselected Abemaciclib + Atezolizumab (Randomized) and CDK12 Mutation Abemaciclib + Atezolizumab (Non-Randomized) Arms

  DLT was assessed by Bayesian Continuous Toxicity Monitoring in Biomarker-Unselected Abemaciclib + Atezolizumab (Randomized) and CDK12 Mutation Abemaciclib + Atezolizumab (Non-Randomized) arms.

  DLTs were collected while participants on treatment. Treatment duration up to 18 months.

Secondary Outcomes (6)

• Clinical Benefit Rate (CBR)

  From treatment initiation to end of treatment, with follow-up for up to 2 years after treatment discontinuation

• Duration of Response (DOR)

  From the date of first documented CR or PR until disease progression or death, or up to 2 years

• Duration of Therapy (DOT)

  From treatment initiation until treatment discontinuation for any reason

• Time to Progression (TTP)

  From treatment initiation until documented disease progression, or assessed up to 2 years

• 12-month Overall Survival (OS)

  12 months

Study Arms (4)

Biomarker-Unselected Abemaciclib Monotherapy (Randomized)

EXPERIMENTAL

Participants in the Biomarker-Unselected Cohort, defined as those whose tumors are not known to have mutations in the CDK12 gene will be randomized to either receive Abemaciclib as monotherapy or in combination with Atezolizumab * Monotherapy : Participants will receive Abemaciclib orally 2x daily

Drug: Abemaciclib

Biomarker-Unselected Abemaciclib + Atezolizumab (Randomized)

EXPERIMENTAL

Participants in the Biomarker-Unselected Cohort, defined as those whose tumors are not known to have mutations in the CDK12 gene will be randomized to either receive Abemaciclib as monotherapy or in combination with Atezolizumab * Combination Therapy: Participants will receive Abemaciclib orally 2x daily and Atezolizumab intravenously Day 1 of each 21-Day cycle

Drug: Abemaciclib; Drug: Atezolizumab

CDK12 Mutation Atezolizumab Monotherapy (Non-Randomized)

EXPERIMENTAL

Participants in the CDK12 Mutation Cohort defined as those whose tumors are known to have mutations in the CDK12 gene are not randomized but are assigned to receive either Atezolizumab monotherapy or in combination with Abemaciclib based on how many participants in this cohort previously received study treatment. Atezolizumab monotherapy will be given to participants 1-5, these participants will receive Atezolizumab intravenously Day 1 of each 21-Day cycle

Drug: Atezolizumab

CDK12 Mutation Abemaciclib + Atezolizumab (Non-Randomized)

EXPERIMENTAL

Participants in the CDK12 Mutation Cohort defined as those whose tumors are known to have mutations in the CDK12 gene are not randomized but are assigned to receive either Atezolizumab monotherapy or in combination with Abemaciclib based on how many participants in this cohort previously received study treatment. Combination Therapy will be given to participants 6-21, these participants will receive Abemaciclib orally 2x daily and Atezolizumab intravenously Day 1 of each 21-Day cycle

Drug: Abemaciclib; Drug: Atezolizumab

Interventions

Abemaciclib DRUG

Taken orally 2x daily

Also known as: Verzenio

Biomarker-Unselected Abemaciclib + Atezolizumab (Randomized); Biomarker-Unselected Abemaciclib Monotherapy (Randomized); CDK12 Mutation Abemaciclib + Atezolizumab (Non-Randomized)

Atezolizumab DRUG

Intravenously Day 1 of 21 day cycle

Also known as: Tecentriq

Biomarker-Unselected Abemaciclib + Atezolizumab (Randomized); CDK12 Mutation Abemaciclib + Atezolizumab (Non-Randomized); CDK12 Mutation Atezolizumab Monotherapy (Non-Randomized)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of metastatic castration resistant prostate cancer (mCRPC), with histologic confirmation of adenocarcinoma of the prostate (without evidence of small cell carcinoma), with progressive disease at the time of study entry by either
• Sequence of at least 2 rising PSA values at a minimum of 1-week intervals
• Radiographic progression per RECIST1.1 for soft tissue and/or per PCWG3 for bone, with or without PSA progression
• Adult males 18 years of age or older.
• ECOG performance status of 0 or 1
• Patients must have metastatic disease by bone scintigraphy or other nodal or visceral lesions on CT or MRI with a bone or soft tissue lesion amenable to image-guided percutaneous biopsy, and the patient must be evaluable for disease response by either
• Baseline PSA ≥ 2.0 ng/mL OR
• Measurable disease per RECIST 1.1
• Past progression or intolerance to at least one novel antiandrogen therapy (abiraterone, enzalutamide, galeterone, apalutamide, darolutamide, orteronel, seviteronel or equivalent) in either the hormone-sensitive or castration-resistant disease setting.
• Not a candidate for docetaxel or cabazitaxel chemotherapy due to:
• progression within 12 months of completion or intolerance to prior taxane OR
• refusal of taxane OR
• contraindication to, or lack of fitness for taxane OR
• Investigator assessment that taxane is not clinically indicated or preferred.
• Maintenance of castration status, defined as serum testosterone level of less than 50 ng/dL. Patients must be surgically castrate or maintained on LHRH agonist or antagonist therapy for the duration of the study period.

You may not qualify if:

• Clinical evidence of, or known and untreated metastatic CNS disease.
• Concurrent active malignancy.
• Patients with non-melanomatous skin cancer, cancer not needing active therapy for at least 2 years, cancer for which the treating investigator deems the subject to be in remission, or any prior malignancy that was treated with curative intent (no evidence of disease for at least 3 years) are also permitted to enroll.
• Patients who have had chemotherapy or radiotherapy within 4 weeks prior to planned cycle 1 day 1 of study treatment.
• Patients who have received oral anti-neoplastic intervention such as an oral hormonal agent, PARP inhibitor, AR targeted therapy, or oral experimental agent within 14 days prior to planned cycle 1 day 1 of study treatment.
• Prior treatment with an inhibitor of CDK4 and/or 6.
• Prior treatment with an inhibitor of PD-1, PD-L1, or PD-L2.
• Patients on concurrent therapy with a moderate or strong CYP3A4 inducer or inhibitor which cannot be safely stopped at least five half-lives prior to initiation of therapy with abemaciclib.
• Evidence of an active autoimmune disease that has required systemic treatment within the last 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Patients with conditions requiring replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) are permitted to enroll.
• Live vaccine within 30 days of registration.
• Active smoking or a history of smoking greater than 20 pack-years (i.e. # packs of cigarettes smoked per day × # of years patient has smoked \> 20).
• Prior history of radiation therapy to thorax (including to lungs/pleura, esophagus, intrathoracic lymph nodes, C7-L2 vertebrae, or ribs) for any reason and any duration/dose.
• Any history of interstitial lung disease, pneumonitis or idiopathic pulmonary fibrosis, regardless of remission or immunosuppression status.
• Any history of lung cancer, regardless of stage or treatment

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Eli Lilly and Company: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

abemaciclib; atezolizumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Atish Choudhury, MD PhD
• Organization: Dana-Farber Cancer Institute

atish_choudhury@dfci.harvard.edu

6176326328

Study Officials

• Atish Choudhury, MD, PhD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 4, 2021
• First Posted: February 12, 2021
• Study Start: August 20, 2021
• Primary Completion: June 17, 2024
• Study Completion: April 30, 2026
• Last Updated: February 20, 2026
• Results First Posted: October 2, 2025

Record last verified: 2026-02

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)