A Study of DeTIL-0255 in Adults With Advanced Malignancies

Study Overview
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Brief Summary
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This is a first-in-human Phase 1 multicenter, open-label oncology study designed to evaluate the safety and efficacy of NX-DeTIL-0255-201 in patients with advanced malignancies.

Detailed Description
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This study includes a safety run in and a cohort expansion. The safety run in will include patients with any of the indications under study including: Recurrent or persistent platinum-resistant epithelial ovarian cancer (EOC), including primary peritoneal and fallopian tube carcinoma Recurrent, metastatic, or persistent cervical carcinoma Advanced or recurrent endometrial cancer Cohort expansion will include patients with advanced malignancies who have received at least two prior systemic therapies in the same indications.

Official Title
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A Phase 1 Safety and Tolerability Study of DeTIL-0255 in Adults With Advanced Malignancies

Conditions
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Platinum-resistant Ovarian Cancer, Endometrial Cancer, Cervical Cancer

Intervention / Treatment
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* Biological: Drug Product De-TIL-0255


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: One of the following malignancies: Recurrent or persistent platinum-resistant EOC, recurrent, metastatic or persistent carcinoma of the cervix with progression after treatment with taxane-containing regimen, or advance or recurrent endometrial cancer with disease progression after or during second line or greater therapy Disease that is metastatic and measurable by RECIST v1.1 criteria A resectable lesion for TIL generation At least 2 prior lines of therapy ≥ 18 years and ≤ 70 years of age Life expectancy of at least 4 months Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Adequate organ and bone marrow function, in the absence of growth factors Patients of child-bearing potential must use adequate contraceptive measures to avoid pregnancy for the duration of the study as defined in the protocol A signed consent form indicating that the subjects understands the purpose and procedures required for the study Exclusion Criteria: Known untreated brain metastases Uncontrolled intercurrent illness History of known seizure disorder Unable to comply with study requirements Toxicities from previous anticancer therapies that have not resolved to baseline levels or to Grade 1 or less except for alopecia and peripheral neuropathy Pregnant, breastfeeding, or planning to become pregnant while enrolled on this study or within 6 months after DeTIL infusion Live vaccine within 28 days of first dose of NMA chemotherapy or planned live vaccination within 6 months following DeTIL infusion Active known second malignancy with the exception of any of the following: Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or adequately treated follicular or papillary thyroid cancer; or any other cancer from which the patient has been disease-free for ≥ 2 years Systemic anti-cancer therapy, including investigational agents, or radiotherapy within 4 weeks of tumor resection Major surgery within 4 weeks before tumor resection, or will not have fully recovered from surgery, or has surgery planned within 8 weeks after infusion Use of systemic corticosteroids within 15 days (or other immunosuppressive drugs within 30 days) prior to tumor resection Use of biotin or other supplements containing higher that the daily adequate intake of biotin Clinically significant, uncontrolled cardiac, class III or IV heart failure, thromboembolic events, cardiovascular disease, or history of myocardial infarction within 6 months of planned start of study drug History or current evidence of anything that might confound the results of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Safety Run In<br>Patients with gynecological malignancies | Biological: Drug Product De-TIL-0255<br>* Autologous tumor-infiltrating lymphocytes<br>|
| Experimental: EOC<br>Recurrent or persistent platinum-resistant epithelial ovarian cancer (EOC), including primary peritoneal and fallopian tube carcinoma | Biological: Drug Product De-TIL-0255<br>* Autologous tumor-infiltrating lymphocytes<br>|
| Experimental: Cervical<br>Recurrent, metastatic, or persistent cervical carcinoma | Biological: Drug Product De-TIL-0255<br>* Autologous tumor-infiltrating lymphocytes<br>|
| Experimental: Endometrial<br>Advanced or recurrent endometrial cancer | Biological: Drug Product De-TIL-0255<br>* Autologous tumor-infiltrating lymphocytes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events | NX-DeTIL-0255-201 | 24 Months | 
| Incidence of all deaths | NX-DeTIL-0255-201 | 24 Months | 
| Incidence of dose limiting toxicities | NX-DeTIL-0255-201 | 24 Months | 
| Objective response rate (ORR) per disease-specific response criteria as assessed by the Investigator | NX-DeTIL-0255-201 | 24 Months | 
| Duration of response (DOR) as assessed by the Investigator | NX-DeTIL-0255-201 | 24 Months | 
| Disease control rate (DCR) as assessed by the Investigator | NX-DeTIL-0255-201 | 24 Months | 
| Progression-free survival (PFS) as assessed by the Investigator | NX-DeTIL-0255-201 | 24 Months | 
| Overall survival (OS) as assessed by the Investigator | NX-DeTIL-0255-201 | 24 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in immune cell infiltration in the tumor following DeTIL-0255 infusion | NX-DeTIL-0255-201 | 24 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ACT, NX-DeTIL-0255, Adoptive Cell Therapy, Tumor Infiltrating Lymphocyte, TIL, DeTIL