KSQ-004EX for Advanced Solid Tumors

Overseen By Rodabe N Amaria, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Aminoglycosides, Penicillin, Steroids, others

Disqualifiers: Autoimmune disorders, Brain metastases, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

141 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called KSQ-004EX (experimental treatment) for individuals with advanced solid tumors. The first part of the trial aims to determine the appropriate dose of the treatment. The second part will assess whether this dose can control the cancer. Individuals with melanoma, lung, head and neck, colorectal, pancreatic, or cervical cancer that has not responded to previous treatments may be suitable candidates. The trial will also evaluate the safety and effects of the treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

The trial requires a 'washout period' (time without taking certain medications) from prior cancer treatments before starting the study. This includes a minimum of 7 days or 5 half-lives for targeted therapies, 21 days or 5 half-lives for monoclonal antibodies, and 21 days or 5 half-lives for chemotherapy. Please discuss with your doctor to understand how this applies to your current medications.

Is there any evidence suggesting that KSQ-004EX is likely to be safe for humans?

Studies are testing KSQ-004EX to determine its safety and effectiveness for people with advanced solid tumors. Researchers are still learning about its effects on humans. In early trials, participants receive KSQ-004EX along with cyclophosphamide and fludarabine, which enhance the treatment by lowering certain white blood cells.

As the trial is in its early and middle stages, researchers focus on how well participants tolerate the treatment and any side effects. Detailed information about specific side effects is not yet available, but this stage emphasizes safety to ensure the treatment is well-tolerated before progressing.

If the treatment had already been approved for another use, it might suggest safety. However, KSQ-004EX remains under study, so researchers closely monitor for any unwanted reactions. The overall goal is to find a safe dose that can help fight tumors while keeping side effects manageable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for advanced solid tumors?

Researchers are excited about KSQ-004EX for advanced solid tumors because it uses a novel approach that combines the drug with lymphodepletion, enhancing the immune system's ability to attack cancer cells. Unlike traditional chemotherapy, which can broadly target both healthy and cancerous cells, KSQ-004EX specifically targets tumor cells, potentially reducing side effects. Additionally, the treatment involves a unique combination of cyclophosphamide and fludarabine as pre-medication to prepare the body by reducing lymphocytes, allowing KSQ-004EX to work more effectively. This innovative approach aims to improve outcomes for patients with advanced solid tumors who have limited options with current therapies.

What evidence suggests that KSQ-004EX might be an effective treatment for advanced solid tumors?

Research has shown that KSQ-004EX may help treat advanced solid tumors. Early studies found that KSQ-004EX enhances immune cell growth, tumor infiltration, and cancer cell destruction. This trial includes different treatment arms where participants will receive KSQ-004EX, with some arms involving additional lymphodepletion strategies. The treatment modifies certain immune cells to improve their cancer-fighting abilities. In lab tests, these enhanced cells successfully located and destroyed tumors. Additionally, the process achieved over 94% effectiveness in editing key proteins, which is believed to enhance the treatment's efficacy. These results suggest KSQ-004EX could be a powerful new option in cancer therapy. ^{6 7 8 9 10}

Who Is on the Research Team?

Rodabe N. Amaria

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with advanced solid tumors who have not responded to standard treatments. Participants must be adults with measurable disease, adequate organ function, and no autoimmune diseases or conditions that suppress the immune system.

Inclusion Criteria

Washout period from prior anticancer therapy

My head or neck cancer has returned or spread and was treated before.

My bone marrow is working well.

Exclusion Criteria

I am on a stable dose of steroids.

I have a narrowed artery in my neck and a history of heavy smoking.

I am not pregnant or nursing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Escalation

Evaluate the safety and tolerability of KSQ-004EX and determine the expansion dose in participants with advanced solid tumors

6 months

Phase 2: Expansion

Assess the anti-tumor activity of KSQ-004EX at the recommended dose in participants with advanced malignant solid tumors

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• KSQ-004EX

Trial Overview The study is testing KSQ-004EX, a therapy using patient's own immune cells modified to target cancer. Phase 1 determines the safe dose; Phase 2 checks if this dose can control tumor growth. Fludarabine and Cyclophosphamide are given before KSQ-004EX to prepare the body.

How Is the Trial Designed?

Group I: Phase 1/Phase 2: Treatment with Lymphodepletion and KSQ-004EX Experimental Treatment 3 Interventions

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

Group II: Phase 1 mLDC: Treatment with Modified Lymphodepletion and KSQ-004EX Experimental Treatment 3 Interventions

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

Group III: Backfill IL-2: Treatment with Lymphodepletion and KSQ-004EX + IL-2 Experimental Treatment 4 Interventions

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

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

KSQ Therapeutics, Inc.

Industry Sponsor

Trials

3

Recruited

410+

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-07763

Genetically Engineered Tumor Infiltrating Lymphocytes ... Giving KSQ-004EX with LDC and IL-2 may be effective in treating patients with advanced solid tumors. Eligibility Criteria ...

2. targetedonc.com targetedonc.com/view/first-patient-receives-ksq-004ex-for-advanced-cancer

First Patient Receives KSQ-004EX for Advanced Cancer We believe these enhancements give KSQ-004EX the potential to significantly advance TIL therapy for the treatment of solid tumors,” said Qasim ...

3. ksqtx.com ksqtx.com/press-releases/ksq-therapeutics-announces-first-patient-dosed-in-phase-1-2-study-for-ksq-004ex-a-crispr-cas9-engineered-tumor-infiltrating-lymphocyte-etil-therapy/

KSQ Therapeutics Announces First Patient Dosed in Phase ... Upon transfer in preclinical solid tumor models, KSQ-004EX demonstrated improved engraftment, expansion, tumor infiltration and killing while ...

4. jitc.bmj.com jitc.bmj.com/content/12/Suppl_2/A513

453 KSQ-004EX: a SOCS1/Regnase-1 dual-edited eTIL ... Results KSQ-004EX on-target editing efficiency was > 94% for both SOCS1 and Regnase-1 with commensurate protein loss. KSQ-004EX displayed a ...

5. curetoday.com curetoday.com/view/first-patient-dosed-with-ksq-004ex-in-solid-tumor-clinical-trial

First Patient Dosed With KSQ-004EX In Solid Tumor ... KSQ-004EX is being evaluated in solid tumors including melanoma, non-small cell lung, head and neck, colorectal, pancreatic and cervical cancer.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS2675

A phase 1/2 study of KSQ-004EX: Autologous tumor ... The phase 1/2, single-arm, open-label study will assess the safety, tolerability, and efficacy of KSQ-004EX in patients with select advanced solid tumors.

7. ksqtx.com ksqtx.com/press-releases/ksq-therapeutics-announces-fda-clearance-of-ind-application-for-ksq-004ex-a-crispr-cas9-engineered-tumor-infiltrating-lymphocyte-etil-therapy/

KSQ Therapeutics Announces FDA Clearance of IND ... Phase 1/2 clinical study will evaluate the safety and preliminary efficacy of KSQ-004EX in advanced solid tumors.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06598371

NCT06598371 | A Phase 1/2 Study of KSQ-004EX, ... Assess the safety and tolerability of KSQ-004EX in participants with advanced solid tumors (melanoma, NSCLC, HNSCC, CRC, pancreatic cancer, and cervical cancer) ...

9. asco.org asco.org/abstracts-presentations/ABSTRACT502112

A phase 1/2 study of KSQ-004EX: Autologous tumor ... The phase 1/2, single-arm, open-label study will assess the safety, tolerability, and efficacy of KSQ-004EX in patients with select advanced solid tumors.

10. ksqtx.com ksqtx.com/pipeline/

Pipeline KSQ-004: Unbiased pair-wise discovery of SOCS1 and Regnase-1 as the top CRISPR/Cas9 dual-edit combination enhancing in vivo TIL potency against solid tumors.