Trial Title:
Open-Label Study to Evaluate the Safety, Tolerability, PK, and Efficacy of INX-315 in Patients With Advanced Cancer
NCT ID:
NCT05735080
Condition:
Breast Cancer
Breast Cancer Metastatic
Hormone Receptor Positive Tumor
Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
Ovarian Cancer
CCNE1 Amplification
Solid Tumor
Advanced Cancer
Metastatic Cancer
Conditions: Official terms:
Neoplasms
Breast Neoplasms
Fulvestrant
Conditions: Keywords:
CDK2
CDK4/6i
cyclin dependent kinase 2
CCNE1
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Intervention model description:
Part A will be a dose escalation guided by BOIN design for treatment assignment and
dosing rules.
Part B will be dose expansion, patients will be randomly assigned to receive one of the
identified doses of INX-315 in monotherapy
Part C will be dose expansion, patients will receive INX-315 in combination treatment
with CDK4/6i and endocrine therapy
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
INX-315
Description:
Oral administration
Arm group label:
Part A INX-315 + Fulvestrant
Arm group label:
Part A: Dose Escalation
Arm group label:
Part B: Ovarian Dose Expansion
Arm group label:
Part C: ER+/HER2- BC Dose Expansion
Intervention type:
Drug
Intervention name:
Fulvestrant
Description:
Fulvestrant will be combined with INX-315
Arm group label:
Part A INX-315 + Fulvestrant
Other name:
faslodex
Summary:
Incyclix Bio (Incyclix) is developing INX-315 as an oral, small molecule inhibitor of
cyclin dependent kinase 2 (CDK2) for the treatment of human cancers. This first-in-human
study is designed to evaluate the safety, tolerability, pharmacokinetics (PK) and
preliminary antitumor activity of INX-315 in patients with recurrent advanced/metastatic
cancer, including hormone receptor positive (HR+)/Human Epidermal Growth Factor Receptor
2 Negative (HER2-) breast cancer who progressed on a prior cyclin-dependent kinase 4/6
inhibitor (CDK4/6i) regimen, and CCNE1-amplified solid tumors who progressed on standard
of care treatment. This study will evaluate approximately 6 dose levels of daily INX-315
in Part A, at least two dose levels will be evaluated in Part B to identify the
Recommended Phase 2 Dose (RP2D) in patients with ovarian cancer, and Part C will evaluate
combination treatment of INX-315 plus a CDK4/6i and selective estrogen receptor degrader
(SERD) in HR+/HER2- breast cancer patients who have progressed on prior CDK4/6i regimen.
Detailed description:
Study INX-315-01 is a first-in-human, Phase 1/2, open-label, dose escalation and
dose-expansion study to evaluate the safety, PK, and preliminary antitumor activity of
INX-315 in patients with advanced/metastatic cancers. The study will be conducted in 3
parts: Part A (dose escalation) and Part B (ovarian cancer dose expansion) and Part C
(breast cancer dose escalation lead-in and expansion).
Part A is the dose-escalation portion of the study to evaluate the safety, tolerability,
and PK of INX-315 monotherapy. Dosing decisions will be guided using a Bayesian optimal
interval (BOIN) design. Up to 60 patients with recurrent advanced/metastatic cancer,
including patients with HR+/HER2- breast cancer who progressed on a prior CDK4/6i
regimen, and solid tumors, including ovarian cancer with known amplification of CCNE1 are
planned to be enrolled in Part A.
Dose-limiting toxicities (DLTs) will be assessed during the first treatment cycle, i.e.,
the first 28 days of treatment (the DLT period). Patients who are evaluable for DLT
assessment are those patients who are enrolled, received ≥80% of the planned study drug
doses and all study visits during the DLT assessment period, and complete the 28-day DLT
period.
Additionally, Part A will have two cohorts that will include INX-315 plus fulvestrant in
HR+/HER2- patients who have have had prior treatment with CDK4/6i.
Part B will expand at least two dose levels determined by the SMC. Part B will enroll
patients with platinum-refractory or platinum-resistant advanced/metastatic ovarian
cancer patients with CCNE1 amplifications. Part B will open for enrollment once the SMC
has selected the dose levels to be evaluated from the Part A portion of the study. Part A
patients cannot re-join or continue the study in Part B. Approximately 30 patients will
be equally randomized to receive one of the dose levels of INX-315.
Part C will be an expansion cohort, patients with ER+/HER2- breast cancer will be
enrolled in this cohort.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Advanced unresectable or metastatic ER+/HER2- BC that has progressed following
treatment with a CDK4/6 inhibitor
2. Advanced/ metastatic platinum-resistant or platinum-refractory epithelial ovarian
cancer (including fallopian tube cancer/primary peritoneal cancer) CCNE1 amplified
tumors that progressed after standard systemic therapy
3. Advanced or metastatic solid tumor with known amplification of CCNE1that has
progressed after standard therapy, been intolerant to or is ineligible for standard
therapy
4. At least one measurable lesion as defined by RECIST v1.1 that has not previously
been irradiated
5. ECOG performance status score of 0 or 1.
6. Adequate organ function as demonstrated by the following laboratory values:
1. Hemoglobin ≥ 9.0 g/dL
2. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
3. Platelet count ≥ 100 × 109/L
4. Estimated glomerular filtration rate (eGFR) of ≥60 mL/min
5. Total bilirubin ≤ 1.5 × ULN; AST and ALT ≤ 2.5 × ULN; ≤ 5 × ULN in the presence
of liver metastases
7. Negative pregnancy test
Exclusion Criteria:
1. Have received previous therapy with a CDK2/4/6 inhibitor or CDK2 inhibitor.
2. Have central nervous system (CNS) metastases or spinal cord compression that is
associated with progressive neurological symptoms or requires corticosteroids
(within 4 weeks of enrollment) to control the CNS disease.
3. Have known intracranial hemorrhage and/or bleeding diatheses.
4. Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis.
5. Have clinically active ongoing interstitial lung disease (ILD) of any etiology,
including drug-induced ILD, and radiation pneumonitis within 28 days prior to
initiation of study treatment.
6. Resting QTcF > 470 msec, a history of prolonged QT syndrome or Torsades de pointes,
or a familial history of prolonged QT syndrome.
7. Uncontrolled, cardiovascular disease (including hypertension) with or without
medication
8. History of other malignancies, except for the following: (1) adequately treated
basal or squamous cell carcinoma of the skin; (2) curatively treated a) in situ
carcinoma of the uterine cervix, b) prostate cancer, or c) superficial bladder
cancer; or (3) other curatively treated solid tumor with no evidence of disease for
≥ 3 years.
9. Known HIV infection, including AIDS-related illness, or have active, uncontrolled
infection (viral, bacterial, or fungal), including tuberculosis, hepatitis B virus,
hepatitis C virus, or COVID-19 infection (symptoms and a positive test result).
10. Requires treatment with a prohibited medication or herbal remedy that cannot be
discontinued at least 2 weeks before the start of study drug administration.
11. Have planned or anticipation of the need for major surgical procedure within 28 days
of the first dose of study drug (procedures such as central venous catheter
placement, tumor needle biopsy, and feeding tube placement are not considered major
surgical procedures).
12. Unwilling or unable to comply with scheduled visits, study drug administration plan,
laboratory tests, or other study procedures and study restrictions.
13. Radical radiotherapy within 28 days prior to study entry or palliative radiotherapy
within 2 weeks prior to study entry.
14. Systemic anti-cancer therapy within 28 days or at least 5 half-lives, whichever is
less, prior to the first dose of the study drug
15. Prior irradiation to > 25% of the bone marrow
16. Previous high-dose chemotherapy requiring prior stem cell transplant
17. Participation in other studies involving investigational drug(s) within 4 weeks
prior to study entry.
18. Known or suspected hypersensitivity to active ingredient/excipients in INX-315 or
fulvestrant.
19. Known difficulty in swallowing or tolerating oral medications, or conditions which
would impair absorption of oral medications such as active inflammatory
gastrointestinal disease, uncontrolled nausea or vomiting (i.e., CTCAE ≥ Grade 3
despite antiemetic therapy), ongoing gastrointestinal obstruction/motility
disorder/active inflammation, malabsorption syndrome, chronic diarrhea, known
diverticular disease or previous gastric resection or lap band surgery.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Emory Winship Cancer Institute
Address:
City:
Atlanta
Zip:
30322
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Kevin M Kalinsky, MD
Email:
Principal Investigator
Facility:
Name:
Dana-Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Alissa Skavish
Email:
Alissa_Skavish@dfci.harvard.edu
Investigator:
Last name:
Antonio Giordano, MD
Email:
Principal Investigator
Facility:
Name:
Levine Cancer Institute (LCI)- Atrium Health
Address:
City:
Charlotte
Zip:
28204
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Antoinette Tan, MD
Email:
Principal Investigator
Facility:
Name:
Duke Cancer Center/ DUMC
Address:
City:
Durham
Zip:
27705
Country:
United States
Status:
Recruiting
Investigator:
Last name:
Carey Anders, MD
Email:
Principal Investigator
Facility:
Name:
Gabrail Cancer Research Center
Address:
City:
Canton
Zip:
44718
Country:
United States
Status:
Recruiting
Contact:
Last name:
Carrie Smith, RN
Email:
csmith@gabrailcancercenter.com
Investigator:
Last name:
Nashat Gabrail, MD
Email:
Principal Investigator
Facility:
Name:
Peter MacCallum Cancer Center
Address:
City:
Parkville
Zip:
3052
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Kim Nayeon
Email:
Nayeon.Kim@petermac.org
Investigator:
Last name:
George Au-Yeung, MD
Email:
Principal Investigator
Facility:
Name:
Mater Hospital
Address:
City:
South Brisbane
Zip:
4101
Country:
Australia
Status:
Recruiting
Investigator:
Last name:
Catjerome Shannon, MD
Email:
Principal Investigator
Start date:
March 28, 2023
Completion date:
June 2026
Lead sponsor:
Agency:
Incyclix Bio
Agency class:
Industry
Source:
Incyclix Bio
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05735080
