Ignite Creation Date:
2024-10-26 @ 3:39 PM
Last Modification Date:
2024-10-26 @ 3:39 PM
Study NCT ID:
NCT06586957
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-04
Brief Title:
A Study with NKT3964 for Adults with AdvancedMetastatic Solid Tumors
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Phase 1 First-in-human Open-label Study to Evaluate the Safety Tolerability PK and Preliminary Anti-tumor Activity of the Novel Oral CDK2 Degrader NKT3964 in Adults with Advancedmetastatic Solid Tumors
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of the Dose Escalation phase of the study is to evaluate the safety tolerability pharmacokinetics PK and preliminary anti-tumor activity to determine the preliminary recommended dose for expansion RDE of NKT3964 in adults with advanced or metastatic solid tumors The goal of the Expansion phase of the study is to evaluate the preliminary anti-tumor activity of NKT3964 at the RDEs based on objective response rate ORR and determine the preliminary recommended Phase 2 dose RP2D
Detailed Description:
Inclusion Criteria
- Must have a pathologically confirmed unresectable advanced or metastatic solid tumor listed below with documented disease progression on last standard treatment Patients must also be refractory to or intolerant of existing therapyies known to provide clinical benefit for their condition
Dose Escalation
1 Ovarian cancer with CCNE1 amplification
2 Endometrial cancer with CCNE1 amplification
3 Gastric cancer gastroesophageal junction GEJ or esophageal adenocarcinoma with CCNE1 amplification
4 Small cell lung cancer SCLC
5 Triple-negative breast cancer TNBC human epidermal growth factor receptor 2 estrogen receptor and progesterone receptor negative
6 Pathologically confirmed HR includes estrogen-receptor or progesterone-receptor and human epidermal growth factor receptor 2 negative HER2- breast cancer BrCa must have progressed following treatment with a CDK46 inhibitor and is not suitable for endocrine therapy
7 Other solid tumors with CCNE1 amplification
Dose Expansion
Part 2A Pathologically confirmed HR and HER2- breast cancer which must have progressed following treatment with a CDK46 inhibitor are not suitable for further endocrine therapy and have had no more than one line of prior systemic chemotherapy in the metastatic setting
Part 2B Platinum resistant or refractory ovarian cancer defined as recurrence 6 months after completing platinum-based regimen with progression on at least one platinum containing therapy with CCNE1 amplification as determined by NGS by local liquid or tissue test
Part 2C Advanced unresectable or metastatic gastric GEJ or esophageal adenocarcinoma with progression on at least one systemic therapy with CCNE1 amplification as determined by NGS by local liquid or tissue test
Measurable disease
Age 18 years
ECOG PS 0-1
Have adequate organ function
Subjects with female reproductive organs must be surgically sterile post-menopausal or if of child-bearing potential must meet pre-specified criteria
Subjects who are capable of insemination must meet pre-specified criteria
Ability to swallow oral medications
Subjects must consent to provide archived tumor tissues and paired tumor biopsy at pretreatment and on-treatment
Exclusion Criteria
Locally advanced solid tumor that is a candidate for curative treatment through radical surgery andor radiotherapy or chemotherapy
History of another malignancy with exceptions
History of lymphohistiocytic or lymphoid hyperplasia hemophagocytic lymphohistiocytosis
Failed to recover from effects of prior anticancer treatment therapy to baseline or Grade 1 severity per CTCAE
Clinically significant cardiovascular event within 6 months prior to start of NKT3964 treatment
Visceral spread with life-threatening complications lymphangitic spread known CNS metastases andor carcinomatous meningitis
Clinically active interstitial lung disease
History of uveitis retinopathy or other clinically significant retinal disease
Active or chronic corneal disorders other active ocular conditions requiring ongoing therapy or any clinically significant corneal disease
Major surgery within 2 months or minor surgery within 10 days before the first dose of NKT3964
Has known human immunodeficiency virus HIV active hepatitis B or C infection
Prior treatment with a selective or nonselective CDK2 inhibitor
Childs-Pugh class B or C cirrhosis or any other clinically significant liver disorder
Radiation therapy within 4 weeks prior to C1D1
- Must have a pathologically confirmed unresectable advanced or metastatic solid tumor listed below with documented disease progression on last standard treatment Patients must also be refractory to or intolerant of existing therapyies known to provide clinical benefit for their condition
Dose Escalation
1 Ovarian cancer with CCNE1 amplification
2 Endometrial cancer with CCNE1 amplification
3 Gastric cancer gastroesophageal junction GEJ or esophageal adenocarcinoma with CCNE1 amplification
4 Small cell lung cancer SCLC
5 Triple-negative breast cancer TNBC human epidermal growth factor receptor 2 estrogen receptor and progesterone receptor negative
6 Pathologically confirmed HR includes estrogen-receptor or progesterone-receptor and human epidermal growth factor receptor 2 negative HER2- breast cancer BrCa must have progressed following treatment with a CDK46 inhibitor and is not suitable for endocrine therapy
7 Other solid tumors with CCNE1 amplification
Dose Expansion
Part 2A Pathologically confirmed HR and HER2- breast cancer which must have progressed following treatment with a CDK46 inhibitor are not suitable for further endocrine therapy and have had no more than one line of prior systemic chemotherapy in the metastatic setting
Part 2B Platinum resistant or refractory ovarian cancer defined as recurrence 6 months after completing platinum-based regimen with progression on at least one platinum containing therapy with CCNE1 amplification as determined by NGS by local liquid or tissue test
Part 2C Advanced unresectable or metastatic gastric GEJ or esophageal adenocarcinoma with progression on at least one systemic therapy with CCNE1 amplification as determined by NGS by local liquid or tissue test
Measurable disease
Age 18 years
ECOG PS 0-1
Have adequate organ function
Subjects with female reproductive organs must be surgically sterile post-menopausal or if of child-bearing potential must meet pre-specified criteria
Subjects who are capable of insemination must meet pre-specified criteria
Ability to swallow oral medications
Subjects must consent to provide archived tumor tissues and paired tumor biopsy at pretreatment and on-treatment
Exclusion Criteria
Locally advanced solid tumor that is a candidate for curative treatment through radical surgery andor radiotherapy or chemotherapy
History of another malignancy with exceptions
History of lymphohistiocytic or lymphoid hyperplasia hemophagocytic lymphohistiocytosis
Failed to recover from effects of prior anticancer treatment therapy to baseline or Grade 1 severity per CTCAE
Clinically significant cardiovascular event within 6 months prior to start of NKT3964 treatment
Visceral spread with life-threatening complications lymphangitic spread known CNS metastases andor carcinomatous meningitis
Clinically active interstitial lung disease
History of uveitis retinopathy or other clinically significant retinal disease
Active or chronic corneal disorders other active ocular conditions requiring ongoing therapy or any clinically significant corneal disease
Major surgery within 2 months or minor surgery within 10 days before the first dose of NKT3964
Has known human immunodeficiency virus HIV active hepatitis B or C infection
Prior treatment with a selective or nonselective CDK2 inhibitor
Childs-Pugh class B or C cirrhosis or any other clinically significant liver disorder
Radiation therapy within 4 weeks prior to C1D1
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None