A Phase 1/2 Study of KSQ-001EX, Autologous Tumor Infiltrating Lymphocytes Engineered to Inactivate the SOCS1 Gene, in Patients With Select Advanced Solid Tumors

NCT06237881 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2023-0571NCI-2024-00734
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if KSQ-001EX is safe to give to participants with advanced forms of solid tumors.

Conditions

Melanoma; Lung Neoplasms; Advanced Solid Tumor; Head and Neck Neoplasms

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year.

Study Arms (3)

Arm 1: Phase 1- Safety Lead-in (Cohort 1)

EXPERIMENTAL

Approximately 6 patients with melanoma, NSCLC or HNSCC will be enrolled in the Safety Lead-in phase of the study with a KSQ-001EX dose.

Drug: KSQ-001EX; Drug: Cyclophosphamide; Drug: Fludarabine

Arm 2: Phase 1- Safety Lead-in (Cohort 2)

EXPERIMENTAL

Patients in Cohort 2 will receive IL-2 dosing (600,000 international units \[IU\]/kg administered every 8 to 12 hours for up to 6 doses, as tolerated).

Drug: KSQ-001EX; Drug: Interleukin-2; Drug: Cyclophosphamide; Drug: Fludarabine

Arm 3: Phase 2- Expansion Phase

EXPERIMENTAL

It is expected that approximately 20 participants will be enrolled in each of the 3 indication specific cohorts.

Drug: KSQ-001EX; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

KSQ-001EX DRUG

Given by IV

Arm 1: Phase 1- Safety Lead-in (Cohort 1); Arm 2: Phase 1- Safety Lead-in (Cohort 2); Arm 3: Phase 2- Expansion Phase

Interleukin-2 DRUG

Given by IV

Also known as: IL-2

Arm 2: Phase 1- Safety Lead-in (Cohort 2)

Cyclophosphamide DRUG

Given by IV

Arm 1: Phase 1- Safety Lead-in (Cohort 1); Arm 2: Phase 1- Safety Lead-in (Cohort 2); Arm 3: Phase 2- Expansion Phase

Fludarabine DRUG

Given by IV

Arm 1: Phase 1- Safety Lead-in (Cohort 1); Arm 2: Phase 1- Safety Lead-in (Cohort 2); Arm 3: Phase 2- Expansion Phase

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with one of the following tumor types:
• Unresectable, incurable and/or metastatic histologically and/or cytologically confirmed melanoma (Stage IIIC/IIID or Stage IV) that has progressed following at least 1 line of prior systemic therapy including treatment with anti-PD-1/PD-L1 inhibitor alone or in combination with anti-CTLA-4 inhibitor or anti-LAG-3 antibody. Note: Up to 5 mucosal melanoma patients can be treated in melanoma expansion cohort only.
• Histologically and/or cytologically confirmed primary diagnosis of NSCLC which has progressed on standard therapy which includes treatment with platinum-based chemotherapy and checkpoint inhibitor therapy (either given in combination or sequentially)
• i. Participants with tumors that have known actionable molecular alteration such as EGFR, ALK, ROS-1, BRAF, RET, MET and KRAS must have progressed on standard directed molecular therapy in addition to platinum-based chemotherapy.
• c. Locally advanced, recurrent and/or metastatic histologically and/or cytologically confirmed HNSCC that has been previously treated with at least 1 and no more than 3 lines of prior therapy
• i. Participants must have received a platinum-containing chemotherapy regimen for the treatment of primary tumor in locally advanced, or metastatic setting.
• ii. Participants must have received an anti-PD-1/PD-L1 as monotherapy or in combination with chemotherapy • Resectable lesion(s) for KSQ-001EX manufacturing (tumor ≥1.5cm2 or at least 5 core biopsies)
• At least 1 measurable lesion per RECIST v1.1 (Eisenhauer 2009) following tumor resection for KSQ-001EX manufacturing Note: Lesions in previously irradiated areas should not be selected as a target lesion unless radiation treatment was ≥ 3 months prior, and there has been demonstrated disease progression in the lesion
• Age: between 18 - 70 years old
• Life expectancy of ≥ 12 weeks
• Recovered to ≤ Grade 1 or Baseline toxicity (except alopecia, neuropathy, and endocrinopathies from prior immunotherapy) from prior therapy (per CTCAE)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate bone marrow function defined as:
• Absolute neutrophil count (ANC) of ≥ 1 × 109/L
• Platelet count of ≥ 100.0 × 109/L

You may not qualify if:

• Prior organ allograft or prior cell therapy that included LDC or myeloablative chemotherapy regimen
• Known hypersensitivity to any component of KSQ-001EX or excipient including dimethyl sulfoxide, human serum albumin, LDC regimen (cyclophosphamide or fludarabine) or IL-2 (as applicable)
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, Grade ≥2 colitis or Crohn's disease\], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis\], rheumatoid arthritis, etc.\]). The following are exceptions to this criterion:
• Participants with vitiligo or alopecia
• Participants with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement and stable doses of steroids after immune-mediated hydrophysitis/adrenal insufficiency
• Any chronic skin condition that does not require systemic therapy
• Participants with celiac disease controlled by diet alone
• Hypersensitivity to antibiotics of the aminoglycoside group (eg, streptomycin, gentamicin) or penicillin
• Active, uncontrolled concurrent infection requiring IV antibiotics present at Screening
• Uveal and/or ocular melanoma
• Large cell neuroendocrine NSCLC (defined as pathology with \> 10% neuroendocrine components)
• Symptomatic and/or untreated brain metastases (of any size or number) including active leptomeningeal or parenchymal metastases. Note: Participants with definitively treated brain metastases may be considered for enrollment if stable (defined as stable for 1-month post-central nervous system directed therapy) and does not require ongoing steroid treatment
• Women who are pregnant or nursing
• Seropositive for human immunodeficiency virus (HIV) 1 or 2 or acquired immunodeficiency syndrome, or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) Note: Participants with positive HCV antibody may be eligible if HCV ribonucleic acid \[RNA\] is undetectable on a quantitative HCV RNA assay, following discussion with the Sponsor
• Any form of primary immunodeficiency (eg, Severe Combined Immunodeficiency Disease)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• KSQ Therapeutics, Inc.: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Melanoma; Lung Neoplasms; Head and Neck Neoplasms

Interventions

Interleukin-2; Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Rodabe N Amaria, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2024
• First Posted: February 2, 2024
• Study Start: January 31, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2029
• Last Updated: February 18, 2026

Record last verified: 2026-02

Locations

US (1)