Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic of CC-95775 in Subjects With Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma

NCT04089527 | Completed Phase 1 FDA Drug

• 3 other identifiers: CC-95775-ST-001U1111-1238-60622019-001092-36
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 5

Brief Summary

CC-95775-ST-001 is an open-label, Phase 1B, dose escalation and expansion study of CC-95775 in subjects with advanced or unresectable solid tumors, including laBCC, and relapsed/ refractory non-Hodgkin's lymphoma (NHL). The dose escalation part (Part A) of the study will explore escalating oral doses of CC-95775 administered on a 4d on/24d off schedule to estimate the MTD of CC-95775. A mTPI-2 will help guide CC-95775 dose escalation decisions with the final decisions made by an SRC. Approximately 20 subjects will be enrolled. The expansion cohort (Part B) will evaluate the safety, PK, PD safety and preliminary activity of CC-95775 in advanced solid tumors, including laBCC. Approximately 20 subjects will be enrolled.

Conditions

Lymphoma, Non-Hodgkin

Keywords

Lymphoma; Non-Hodgkin's Lymphoma; CC-95775; Solid Tumors; Safety; Relapsed/Refractory

Outcome Measures

Primary Outcomes (4)

• Dose Limiting Toxicity (DLT)

  is defined as any toxicities occurring within the DLT assessment unless the event can clearly be determined to be unrelated to CC-95775.

  C1 Up to approximately 28 days

• Maximum Tolerated Dose (MTD)

  dose level that could be given such that the estimated DLT probability is closest to 25%.

  Part A of the study- estimated 12 months

• Non-tolerated Dose (NTD)

  The dose that is higher than MTD

  Part A of the study-estimated 12 months

• Adverse Events (AEs)

  Number of participants with adverse event. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study

  From signature of the informed consent until at least 28 days after the last dose of study treatment

Secondary Outcomes (7)

• Pharmacokinetics - Cmax of CC-95775

  Part A and part B of the study, estimated 24 months total

• Pharmacokinetics - AUC of CC-95775

  Part A and part B of the study, estimated 24 months total

• Pharmacokinetics - Tmax of CC-95775

  Part A and part B of the study, estimated 24 months total

• Pharmacokinetics - t1/2 of CC-95775

  Part A and part B of the study, estimated 24 months total

• Pharmacokinetics - CL/F of CC-95775

  Part A and part B of the study, estimated 24 months

Study Arms (1)

CC-95775

EXPERIMENTAL

Escalating dose finding part A of study and extension Part B of the study. In Part A, subjects will be treated with oral capsules of CC-95775 with a schedule of 4d on/ 24d off (Q4W) and a starting dose of 100 mg/day on a 28-day cycle. Dose increments between cohorts will not exceed 100% of the dose in previous cohort. Patients in Part B will be treated with a schedule of 4d on/24d off (Q4W) at the Maximum tolerated dose (MTD) established from Part A.

Drug: CC-95775

Interventions

CC-95775 DRUG

CC-95775

CC-95775

Eligibility Criteria

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

You may qualify if:

• Subjects must satisfy the criteria below to be enrolled in dose escalation (Part A) and in dose expansion (Part B) of this study.
• Men and women ≥ 18 years of age, at the time of signing the ICF.
• Subject must understand and voluntarily sign an ICF prior to any study-specific assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• Subjects with histological or cytological confirmation of either:
• Advanced or unresectable ST, laBCC or R/R NHL.
• Subjects with solid tumors including those who have progressed on (or not been able to tolerate due to medical comorbidities or unacceptable toxicity) standard anticancer therapy or for whom no other approved conventional therapy exists.
• Subjects with laBCC must have unresectable disease which must have progressed after treatment with a smoothened inhibitor (SMOi) or who are intolerant of SMOi on (or not been able to tolerate due to medical comorbidities or unacceptable toxicity).
• For relapsed/ refractory NHL following at least 2 prior lines of therapy (e.g. subjects have failed at least one line of standard therapy and have received at least one prior line of salvage therapy) OR have failed at least one prior line of standard therapy and are not eligible for autologous stem cell transplant (ASCT) OR have declined ASCT; transformed lymphoma following chemotherapy for lower grade lymphoma and at least one standard treatment regimen for DLBCL.
• Subjects with two or more lines of systemic therapy who have been treated with and have lack of response or have responded and relapsed after chimeric antigen receptor T-cell (CAR-T) therapy, if such therapy is available, OR are ineligible for CAR-T therapy at the time of enrollment, OR declined CAR-T therapy.
• Subjects must have at least one site of measurable disease according to RECIST 1.1 Previously irradiated lesions are not considered evaluable; for subjects with R/R NHL, bi-dimensionally measurable disease on cross sectional imaging by CT or MRI, with at least one lesion \>1.5 cm in its greatest transverse diameter, as defined by the IWG criteria. For subjects with rare malignancies, not falling into the above categories and who might benefit from a treatment with BET inhibitor, evaluable disease can be considered.
• Subjects consent to tumor archive material analysis. Tumor biopsies to be collected whenever safe and feasible will be collected in Part A. Subjects consents to mandatory tumor biopsies (Screening and on treatment) in Part B.
• ECOG PS of 0 to 1.
• Subjects must have the following laboratory values at Screening:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without growth factor support for 7 days (14 days if subject received peg-filgrastim).

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment (in Part A and Part B):
• Subject has received anti-cancer therapy (either approved or investigational) within ≤ 4 weeks or 5 half-lives, whichever is shorter, prior to starting CC-95775.
• \< 42 days for prior nitrosureas or mitomycin C
• Toxicities resulting from prior systemic cancer therapies must have resolved to ≤ NCI CTCAE Grade 1 prior to starting CC-95775 treatment (with exception of Grade 2 peripheral neuropathy and alopecia).
• Subject has received autologous hematologic stem cell transplant (HSCT) ≤ 3 months prior to starting CC-95775 treatment. Subjects with allogeneic HSCT will not be allowed on this protocol.
• Subject has undergone major surgery ≤ 4 weeks or minor surgery ≤ 2 weeks prior to starting CC-95775 or who have not recovered from surgery.
• Subject has completed any radiation treatment \< 4 weeks prior to starting CC-95775 (with exception of palliative bone radiotherapy for which 2-week period is required).
• Subject has persistent diarrhea due to a malabsorptive syndrome (such as celiac sprue or inflammatory bowel disease) ≥ NCI CTCAE Grade 2, despite medical management, or any other significant GI disorder that could affect the absorption of CC-95775.
• Subjects with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and GI tract hemorrhages.
• Subjects with symptomatic or uncontrolled diabetes mellitus.
• Symptomatic, untreated, or unstable central nervous system (CNS) metastases, (except in case of CNS primary tumors).
• Subjects recently treated with whole brain radiation or stereotactic radiosurgery for CNS metastases must have completed therapy at least 4 weeks prior to starting CC-95775 and have a follow-up brain CT or MRI demonstrating either stable or improving metastases 4 or more weeks after completion of radiotherapy (the latter to be obtained as part of the Screening Assessments.
• Subjects must be asymptomatic and off steroids or on stable dose of steroids for at least 4 weeks (\<4 mg/day dexamethasone or equivalent) or on tapering dose of steroids.
• Known symptomatic acute or chronic pancreatitis.
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

Sponsors & Collaborators

• Celgene: lead

Study Sites (5)

Institut Curie

Paris, 75005, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Centre Eugene Marquis

Rennes, 35200, France

Location

Hospital de Madrid Norte- Sanchinarro

Madrid, 28050, Spain

Location

Clinica Universidad de Navarra

Pamplona, 31008, Spain

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma; Recurrence

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Pilar Lardelli, MD PhD

  Celgene

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2019
• First Posted: September 13, 2019
• Study Start: October 24, 2019
• Primary Completion: October 25, 2021
• Study Completion: October 25, 2021
• Last Updated: February 1, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

FR (3); ES (2)