A Study With NKT3964 for Adults With Advanced/Metastatic Solid Tumors
- Conditions
- Solid TumorAdvanced Solid TumorSolid Tumor, AdultMetastatic TumorOvarian CancerOvarian NeoplasmsOvarian CarcinomaMetastatic Ovarian CarcinomaEndometrial NeoplasmsEndometrial Diseases
- Interventions
- Registration Number
- NCT06586957
- Lead Sponsor
- NiKang Therapeutics, Inc.
- 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 therapy(ies) 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 CDK4/6 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 CDK4/6 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 and/or 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 and/or 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
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 90
- 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 therapy(ies) known to provide clinical benefit for their condition.
Dose Escalation:
- Ovarian cancer with CCNE1 amplification
- Endometrial cancer with CCNE1 amplification
- Gastric cancer, gastroesophageal junction (GEJ) or esophageal adenocarcinoma with CCNE1 amplification
- Small cell lung cancer (SCLC)
- Triple-negative breast cancer (TNBC; human epidermal growth factor receptor 2, estrogen receptor and progesterone receptor negative)
- 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 CDK4/6 inhibitor, and is not suitable for endocrine therapy)
- 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 CDK4/6 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.
- Have adequate organ function
- Subjects with female reproductive organs must be surgically sterile, post-menopausal, or must be willing to use highly effective method(s) of contraception
- Ability to swallow oral medications.
- Subjects must consent to provide archived tumor tissues and paired tumor biopsy at pretreatment
- Locally advanced solid tumor that is a candidate for curative treatment through radical surgery and/or 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 and/or 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation NKT3964 Dose escalation will assess the safety, efficacy, and PK/PD data of oral dosing NKT3964 at increasing dosage levels to determine the MTD and/or preliminary RDEs. Dose Expansion NKT3964 Dose expansion will include 2 RDEs selected to determine the preliminary antitumor activity and the RP2D.
- Primary Outcome Measures
Name Time Method Number of Participants with Dose Limiting Toxicity (DLT) events 28 Days DLTs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
Objective Response Rate (ORR) 1 Year ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as determined by the Investigator
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) 2 Year PFS defined as the time from the date the participant started study drug to the date the participant experiences an event of disease progression or death.
Duration of Response (DOR) 2 Year Duration of overall response is defined as the time from the date of first documented CR or PR, assessed by investigator and based on RECIST v. 1.1, to the documented date of progressive disease (PD) or death, whichever occurred first.
Disease control rate 1 Year Disease control rate defined as CR + PR + stable disease \[SD\]
Overall Survival (OS) 2 Year OS defined as the time from the date the participant started study drug to death for any reason.
Time to Response (TTR) 1 Year TTR is defined as the time from first dose to the first documented CR or PR which is subsequently confirmed.
Number of Participants with Adverse Events 2 Year An adverse event (AE) is defined as any untoward medical occurrence in a patient and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related.
Maximum observed plasma concentration (Cmax) of NKT3964 1 Month Maximum observed plasma concentration (Cmax) of NKT3964
Time to maximum observed plasma concentration of NKT3964 (Tmax) 1 Month Time to maximum observed plasma concentration of NKT3964 (Tmax)
Observed trough concentration of NKT3964 (Ctrough) 88 Weeks Observed trough concentration of NKT3964 (Ctrough)
Area under the plasma concentration-time curve (AUC0-t) of NKT3964 1 Month Area under the plasma concentration-time curve (AUC0-t) of NKT3964
Apparent clearance (CL/F) 1 Month Apparent clearance (CL/F)
Apparent volume of distribution (V/F) 1 Month Apparent volume of distribution (V/F)
Half-life (t1/2) 1 Month Half-life (t1/2)
Accumulation ratio (AR) 1 Month Accumulation ratio (AR)
Trial Locations
- Locations (8)
University of Arkansas Medical School
🇺🇸Little Rock, Arkansas, United States
Florida Cancer Specialists & Research Institute
🇺🇸Lake Mary, Florida, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
John Theurer Cancer Center at Hackensack UMC
🇺🇸Hackensack, New Jersey, United States
Sidney Kimmell Cancer Center - Jefferson Health
🇺🇸Philadelphia, Pennsylvania, United States
Sarah Cannon Research Institute (SCRI)
🇺🇸Nashville, Tennessee, United States
NEXT Oncology
🇺🇸Austin, Texas, United States
Intermountain Health
🇺🇸Salt Lake City, Utah, United States