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Clinical trial information and results are updated daily from ClinicalTrials.gov. The latest data update was conducted on 01/20/2021.

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

Clinicaltrials.gov identifier NCT04089527

Recruitment Status Recruiting

First Posted September 13, 2019

Last update posted February 26, 2020

Study Description

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.

  • Condition or Disease:Lymphoma, Non-Hodgkin
  • Intervention/Treatment: Drug: CC-95775
  • Phase: Phase 1
Detailed Description

N/A

Study Design
  • Study Type: Interventional
  • Estimated Enrollment: 40 participants
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label) ()
  • Primary Purpose: Treatment
  • Official Title: A Phase 1B Dose Escalation, Multicenter, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic of CC-95775 in Subjects With Advanced Solid Tumors and Relapsed/Refractory Non-hodgkin's Lymphoma
  • Actual Study Start Date: October 2019
  • Estimated Primary Completion Date: June 2023
  • Estimated Study Completion Date: June 2023
Arms and interventions
Arm Intervention/treatment
Experimental: CC-95775
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
CC-95775
Outcome Measures
  • Primary Outcome Measures: 1. Dose Limiting Toxicity (DLT) [ Time Frame: C1 Up to approximately 28 days ]
    is defined as any toxicities occurring within the DLT assessment unless the event can clearly be determined to be unrelated to CC-95775.
  • 2. Maximum Tolerated Dose (MTD) [ Time Frame: Part A of the study- estimated 12 months ]
    dose level that could be given such that the estimated DLT probability is closest to 25%.
  • 3. Non-tolerated Dose (NTD) [ Time Frame: Part A of the study-estimated 12 months ]
    The dose that is higher than MTD
  • 4. Adverse Events (AEs) [ Time Frame: From signature of the informed consent until at least 28 days after the last dose of study treatment ]
    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
  • Secondary Outcome Measures: 1. Pharmacokinetics - Cmax of CC-95775 [ Time Frame: Part A and part B of the study, estimated 24 months total ]
    Maximum plasma concentration of drug
  • 2. Pharmacokinetics - AUC of CC-95775 [ Time Frame: Part A and part B of the study, estimated 24 months total ]
    Area under the curve
  • 3. Pharmacokinetics - Tmax of CC-95775 [ Time Frame: Part A and part B of the study, estimated 24 months total ]
    Time to peak plasma concentration
  • 4. Pharmacokinetics - t1/2 of CC-95775 [ Time Frame: Part A and part B of the study, estimated 24 months total ]
    Half-life the time it takes for the concentration of the drug in the plasma to be reduced by 50%
  • 5. Pharmacokinetics - CL/F of CC-95775 [ Time Frame: Part A and part B of the study, estimated 24 months ]
    Measurement of the volume of plasma from which a substance is completely removed per unit time
  • 6. Pharmacokinetics - Vz/F of CC-95775 [ Time Frame: Part A and part B of the study, estimated 24 months ]
    Apparent volume of distribution. It is the volume needed to account for the total amount of drug in the body if the drug was evenly distributed throughout the body and in the same concentration as the site of sample collection such as peripheral venous plasma
  • 7. Evaluate the pharmacodynamic (PD) effects of CC-95775 on gene expression in peripheral blood and in tumor tissue. [ Time Frame: Part B of the study, estimated 12 months ]
    Changes in the expression of genes associated to BET inhibitors in PBMCs and/or other genes, such as GLI1, MYC, in tumor biopsy may provide confirmation that a dose is pharmacologically active and enable identification of dose, which results in optimal target engagement
Eligibility Criteria
  • Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No
Criteria

Inclusion Criteria:

Subjects must satisfy the criteria below to be enrolled in dose escalation (Part A) and in
dose expansion (Part B) of this study.

1. Men and women ≥ 18 years of age, at the time of signing the ICF.

2. Subject must understand and voluntarily sign an ICF prior to any study-specific
assessments/procedures being conducted.

3. Subject is willing and able to adhere to the study visit schedule and other protocol
requirements.

4. 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.

5. 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.

6. ECOG PS of 0 to 1.

7. 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).

- Hemoglobin (HGB ≥10 g/dL (≥ 8g/dL for DLBCL subjects).

- Platelet count (PLT) ≥150 x 109/L (≥100 x 109/L without transfusion for 7 days
for DLBCL subjects).

- Serum potassium concentration within normal range, or correctable with
supplements

- Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST)
and serum glutamate pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) ≤
3.0 x Upper Limit of Normal (ULN).

- Serum total bilirubin ≤ 1.5 x ULN.

- Serum creatinine ≤ 1.5 x ULN or measured glomerular filtration rate (GFR) ≥ 50
mL/min/1.73 m2 using an exogenous filtration marker such as iohexol, inulin, 51Cr
EDTA or 1125 iothalamate, or creatinine clearance of ≥ 50 mL/min using
Cockroft-Gault equation.

- Subjects must have serum albumin > 3.5 g/dL.

- PT (or INR) and APTT within normal range.

8. Subjects must agree not to share study drugs with another person

9. Females of childbearing potential

- A female of childbearing potential (FCBP) is a female who: 1) has achieved
menarche at some point, 2) has not undergone a hysterectomy or bilateral
oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following
cancer therapy or other medical condition does not rule out childbearing
potential) for at least 12 consecutive months and verified by an FSH blood test
at screening.

- FCBP must either commit to true abstinence from heterosexual intercourse (which
must be reviewed monthly and source documented) or to use one highly effective
contraceptive method plus one barrier method. True abstinence is acceptable when
this is in line with the preferred and usual lifestyle of the subject. (Periodic
abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and
withdrawal are not acceptable methods of contraception). Highly effective
contraceptive methods are combined (containing estrogen and progestogen) or
progestogen-only hormonal contraception associated with inhibition of ovulation
(oral, injectable, intravaginal, patch, or implantable); bilateral tubal
ligation; intrauterine device; intrauterine hormone-releasing system; or
vasectomized partner sterilization (note that vasectomized partner is a highly
effective birth control method provided that partner is the sole sexual partner
of the FCBP trial participant and that the vasectomized partner has received
medical assessment of the surgical success). Barrier methods are male or female
latex or synthetic condom, diaphragm, cervical cap or sponge with spermicide,
barrier contraceptive with spermicide. These measures should be used from signing
the ICF, throughout the study, and for up to 44 days following the last dose of
CC-95775.

- Have two negative pregnancy tests as verified by the investigator prior to
starting CC-95775.

- Pregnancy testing:

- A negative serum pregnancy test (or β-subunit of human chorionic gonadotropin
(β-hCG pregnancy test) at Screening verified by the Investigator.

- A negative serum or urine pregnancy test (or β-subunit of human chorionic
gonadotropin (β-hCG pregnancy test) on Day 1 of dosing verified by the
Investigator prior to dosing.

- Agree to ongoing pregnancy testing during the course of the study, and after the
end of study treatment. This applies even if the subject practices true
abstinence from heterosexual contact.

10. Male subjects must practice true abstinence (which must be reviewed on a monthly
basis) or agree to use a condom (a latex or non-latex synthetic condom is required)
during sexual contact with a pregnant female or a FCBP and will avoid conceiving from
signing the ICF, while participating in the study, during dose interruptions, and for
at least 104 days following CC-95775 discontinuation, even if he has undergone a
successful vasectomy. True abstinence is acceptable when this is in line with the
preferred and usual lifestyle of the subject [female partner's periodic abstinence
(e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are
not acceptable methods of contraception].

- Males must agree not to donate semen or sperm for at least 104 days following
CC-95775 discontinuation.

- Other than the subject, FCBP and males able to father a child should not handle
the study drugs or touch the capsules, unless gloves are worn.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment (in Part A and
Part B):

1. 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 2. 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). 3. 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. 4. Subject has undergone major surgery ≤ 4 weeks or minor surgery ≤ 2 weeks prior to starting CC-95775 or who have not recovered from surgery. 5. 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). 6. 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. 7. Subjects with symptomatic or uncontrolled ulcers (gastric or duodenal), particularly those with a history of and/or risk of perforation and GI tract hemorrhages. 8. Subjects with symptomatic or uncontrolled diabetes mellitus. 9. 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. 10. Known symptomatic acute or chronic pancreatitis. 11. Impaired cardiac function or clinically significant cardiac diseases, including any of the following: - LVEF CTCAE Grade
2 or hemoptysis > 1 teaspoon within 4 weeks prior to the first dose

19. Subject has any significant medical condition (e.g., active or uncontrolled infection
or renal disease), laboratory abnormality, or psychiatric illness that would prevent
the subject from participating (or compromise compliance) in the study or would place
the subject at unacceptable risk if he/she were to participate in the study.

20. Subject has any condition that confounds the ability to interpret data from the study.

21. Subjects with poor bone marrow reserve as assessed by the Investigator such as in the
following conditions:

- Having received extensive bone radiotherapy

- Having experienced several episodes of bone marrow aplasia in previous treatments

- Confirmed histological bone marrow cancer infiltration (with exemption of NHL)

- Requiring regular hematopoietic support (blood transfusion, erythropoietin,
G-CSF)

22. Subjects with severely compromised pulmonary function and/or requiring chronic oxygen
administration

Contacts and Locations
Contacts

Contact: Pilar Lardelli, MD PhD 34 605209083 plardelli@celgene.com

Contact: Zariana Nikolova, MD PhD 41 327298441 znikolova@celgene.com

Locations

France
Hopital Saint Louis
Paris

France
Centre Eugene Marquis
Rennes

France
Institut Curie
Paris

Spain
Hospital de Madrid Norte- Sanchinarro
Madrid

Spain
Clinica Universidad de Navarra
Pamplona

Sponsors and Collaborators

Celgene

Investigators

Study Director: Pilar Lardelli, MD PhD Celgene

More Information
  • Responsible Party: Celgene
  • ClinicalTrials.gov Identifier: NCT04089527 History of Changes
  • Other Study ID Numbers: CC-95775-ST-001, U1111-1238-6062, 2019-001092-36
  • First Posted: September 13, 2019 Key Record Dates
  • Last Update Posted: February 26, 2020
  • Last Verified: February 2020
  • Individual Participant
    Data (IPD) Sharing
    Statement:
  • Plan to Share IPD: Yes
  • Plan Description: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
  • Supporting Materials: Study Protocol, Statistical Analysis Plan (SAP), Informed Consent Form (ICF), Clinical Study Report (CSR), Analytic Code
  • Time Frame: See Plan Description
  • Access Criteria: See Plan Description
  • URL: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/
  • 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
  • Keywords provided by Celgene: Lymphoma
    Non-Hodgkin's Lymphoma
    CC-95775
    Solid Tumors
    Safety
    Relapsed/Refractory
  • Additional relevant MeSH terms: Lymphoma Lymphoma, Non-Hodgkin