A Phase 1/2 Study of KSQ-004EX, Autologous Tumor Infiltrating Lymphocytes Engineered to Inactivate Genes Encoding SOCS1 and Regnase-1, in Patients With Select Advanced Solid Tumors

NCT06598371 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2024-0397NCI-2024-07763
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 1

Brief Summary

Phase 1 is to find the recommended dose of KSQ-004EX to give to participants with advanced solid tumors. Phase 2 is to learn if KSQ-004EX at the recommended dose found in Phase1 can help to control advanced solid tumors. The safety and effects of KSQ-004EX will also be studied in both phases.

Conditions

Select Advanced Solid Tumors

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)

Backfill IL-2: Treatment with Lymphodepletion and KSQ-004EX + IL-2

EXPERIMENTAL

Participants will receive KSQ-004EX and pre-medicated with cyclophosphamide and fludarabine to prevent the lymphodepletion of the chemotherapy.

Drug: Cyclophosphamide; Drug: Fludarabine; Drug: KSQ-004EX; Drug: Interleukin-2

Phase 1 mLDC: Treatment with Modified Lymphodepletion and KSQ-004EX

EXPERIMENTAL

Participants will receive KSQ-004EX and pre-medicated with cyclophosphamide and fludarabine to prevent the lymphodepletion of the chemotherapy.

Drug: Cyclophosphamide; Drug: Fludarabine; Drug: KSQ-004EX

Phase 1/Phase 2: Treatment with Lymphodepletion and KSQ-004EX

EXPERIMENTAL

Participants will receive KSQ-004EX and pre-medicated with cyclophosphamide and fludarabine to prevent the lymphodepletion of the chemotherapy.

Drug: Cyclophosphamide; Drug: Fludarabine; Drug: KSQ-004EX

Interventions

Cyclophosphamide DRUG

Given by IV

Backfill IL-2: Treatment with Lymphodepletion and KSQ-004EX + IL-2; Phase 1 mLDC: Treatment with Modified Lymphodepletion and KSQ-004EX; Phase 1/Phase 2: Treatment with Lymphodepletion and KSQ-004EX

Fludarabine DRUG

Given by IV

Backfill IL-2: Treatment with Lymphodepletion and KSQ-004EX + IL-2; Phase 1 mLDC: Treatment with Modified Lymphodepletion and KSQ-004EX; Phase 1/Phase 2: Treatment with Lymphodepletion and KSQ-004EX

KSQ-004EX DRUG

Given by IV

Backfill IL-2: Treatment with Lymphodepletion and KSQ-004EX + IL-2; Phase 1 mLDC: Treatment with Modified Lymphodepletion and KSQ-004EX; Phase 1/Phase 2: Treatment with Lymphodepletion and KSQ-004EX

Interleukin-2 DRUG

Given by IV

Also known as: IL-2

Backfill IL-2: Treatment with Lymphodepletion and KSQ-004EX + IL-2

Eligibility Criteria

• Age: 18 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 cutaneous, acral, or unknown primary melanoma (Stage IIIC or Stage IV) that has progressed following at least 1 and no more than 3 lines of prior therapy in the advanced/metastatic setting, one of which includes treatment with anti-PD-1/PD-L1 inhibitor alone or in combination with anti-cytotoxic T lymphocyte associated protein 4 (anti-CTLA-4) inhibitor or in combination with anti-LAG-3 antibody.
• Note: Up to 5 mucosal patients can be treated in the melanoma expansion cohort only.
• Histologically and/or cytologically confirmed primary diagnosis of NSCLC which has progressed on at least 1 line and no more than 4 lines of prior therapy in the advanced/metastatic setting, including 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 epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS-1, B-Raf proto-oncogene (BRAF), rearranged during transfection (RET), MET and Kirsten Rat Sarcoma Virus (KRAS) must have progressed on standard directed molecular therapy in addition to platinum-based chemotherapy.
• Note, the following do not count towards a line of prior therapy:
• Any therapy/regimen discontinued due to intolerance/tolerability issues
• Retreatment with the same class or previous class of treatment alone or in combination 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 4 lines of prior therapy in the advanced/metastatic setting.
• i. Participants must have received a platinum-containing chemotherapy regimen for the treatment of primary tumor in locally advanced, or metastatic setting d. Advanced, metastatic histologically and/or cytologically confirmed colorectal adenocarcinoma that has progressed following at least 1 and no more than 3 lines of prior therapy. Participants with dMMR/MSI-H or KRASG12C BRAF V600E mutation must have progressed on standard directed therapy.
• e. Locally advanced, recurrent, or metastatic histologically and/or cytologically confirmed pancreatic ductal adenocarcinoma (PDAC) that has progressed following at least 1 and no more than 3 lines of prior therapy in the advanced/metastatic setting.
• f. Recurrent, metastatic, or persistent histologically and/or cytologically confirmed squamous cell carcinoma (SCC), adenosquamous carcinoma, or adenocarcinoma of the cervix that is not amenable to curative treatment with surgery and/or radiation therapy that has progressed following at least 1 and no more than 3 lines of prior therapy in the advanced/metastatic setting.
• Resectable lesion for KSQ-004EX manufacturing (tumor ≥ 1.5 cm2 or at least 5 core needle biopsies)
• At least one measurable lesion per RECIST v1.1 (Eisenhauer 2009) following tumor resection for KSQ-004EX 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 ≥ 18 years of age
• Life expectancy of ≥ 12 weeks

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-004EX 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
• 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) after discussion with the drug provider (KSQ)
• Participants with ascites
• Women who are pregnant or nursing

Sponsors & Collaborators

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

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

Cyclophosphamide; fludarabine; Interleukin-2

Intervention Hierarchy (Ancestors)

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

Study Officials

• Rodabe N Amaria, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rodabe N Amaria, MD

CONTACT

713-792-2921; rnamaria@mdanderson.org

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: September 13, 2024
• First Posted: September 19, 2024
• Study Start: November 21, 2024
• Primary Completion (Estimated): August 1, 2039
• Study Completion (Estimated): August 1, 2041
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

US (1)