CELLO-1: A Phase 1b/2 Open-Label Study Evaluating Tazemetostat in Combination with Enzalutamide or Abiraterone/Prednisone In Chemotherapy Naïve Subjects with Metastatic Castration Resistant Prostate Cancer

Protocol # :
Metastatic Prostate Cancer
Metastatic Castration-resistant Prostate Cancer
Disease Sites
Principal Investigator
Taplin, Mary-Ellen
Site Research Nurses
Aspinwall, Sheridan
Bretta, Katherine, v.
Carey, Margaret, M.
Healy, Erin, C.
Katica, Dean
Lagerstedt, Elizabeth
Leisner, Claire
Mingrino, Sage
Pace, Amanda
Prisby, Judith
Walsh, Meghara

Trial Description

This is a global, multi-center, open-label, randomized phase 1b/2, active-controlled safety
and efficacy study of oral administration of tazemetostat in combination with enzalutamide or
abiraterone/prednisone (phase 1b) versus enzalutamide or abiraterone/prednisone alone in
asymptomatic or mildly symptomatic subjects with progressive, metastatic castration-resistant
prostate cancer (mCRPC) who have progressed on either abiraterone acetate, enzalutamide, or
apalutamide or who are second generation anti-androgen treatment naive, and who have not
received chemotherapy for mCRPC.

This study is designed to determine the recommended phase 2 doses (RP2D) of tazemetostat in
combination with either enzalutamide or abiraterone/prednisone, based on safety,
tolerability, pharmacokinetic, pharmacodynamic, and efficacy profiles.

Eligibility Requirements

Inclusion Criteria:

1. Age at the time of consent ≥ 18 years.

2. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 (Appendix

3. Life expectancy of > 3 months.

4. Histologically or cytologically confirmed adenocarcinoma of the prostate. Small cell
or neuroendocrine tumors of the prostate are also permitted.

5. Progressive disease in the setting of medical or surgical castration (ie, castration-
resistant prostate cancer [CRPC]) by PCWG3 criteria for study entry.

- Evidence of disease progression by rising PSA or

- Soft tissue progression per RECIST 1.1 or

- Evidence of disease progression by observation of 2 new bone lesions since the
initiation of last systemic therapy.

6. Metastatic prostate cancer disease, documented by the following imaging

• Bone lesions on bone scan (per PCWG3) or by soft tissue disease (per RECIST 1.1) by
CT/MRI imaging Must have undergone bilateral orchiectomy or be willing to continue
GnRH analogue or antagonist.

7. Prior treatment with a second-generation androgen inhibitor as follows:

- For phase 1b, EITHER Previously untreated with or progressed on a second
generation androgen inhibitor (abiraterone, enzalutamide, or apalutamide) OR
progressed on a second generation inhibitor (inhibitor (abiraterone,
enzalutamide, or apalutamide)

- For phase 2 randomized component (i.e, enzalutamide- containing treatment arms)
of the study, previously progressed on abiraterone.

Exclusion Criteria:

1. Known symptomatic brain metastases

2. Treatment with any of the following for prostate cancer within the indicated timeframe
prior to day 1 of starting study treatment:

- First generation: AR antagonists (eg, bicalutamide, nilutamide, flutamide) within
4 weeks.

- 5-alpha-reductase inhibitors, ketoconazole, estrogens (including
diethylstilbesterol), or progesterones within 2 weeks.

- Chemotherapy (except as permitted in inclusion criteria #10) within 3 weeks.

- Prior radionuclide therapy within 4 weeks.

- Another interventional product or standard agent in a clinical study within 28
days prior to the first planned dose of Tazemetostat

- For phase 2 subjects to be randomized to one of the enzalutamide treatment arms
only, prior treatment with the second-generation androgen antagonist including
enzalutamide, apalutamide, darolutamide, and proxalutamide, etc.

3. Severe concurrent disease, infection, or comorbidity that, in the judgment of the
Investigator, would make the subject inappropriate for enrollment

4. Has had prior exposure to tazemetostat or other inhibitor(s) of enhancer of zeste