A Phase 1 Study of KSQ-4279 Alone and in Combination in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a Phase 1 study to assess the safety and clinical activity of KSQ-4279 alone and in combination in patients with advanced solid tumors.

Detailed Description
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This is a Phase 1 study consisting of 2 parts: Dose Escalation and Expansion to evaluate the safety, tolerability, clinical activity, and pharmacokinetics (PK) Study of KSQ-4279 as a Monotherapy or in Combination in Patients with Advanced Solid Tumors.

Official Title
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A Phase 1 Study of KSQ-4279 Alone and in Combination in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: KSQ-4279 Monotherapy (Dose Escalation and Expansion)
* Drug: KSQ-4279 Combination Therapy (Dose Escalation and Expansion)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Life expectancy of ≥ 12 weeks Measurable disease or non-measurable per RECIST v1.1 in dose escalation only; patients in dose expansion are required to have measurable disease per RECIST v1.1 Recovered to ≤ Grade 1 or baseline toxicity (except alopecia) from prior therapy (per NCI-CTCAE v5.0) Eastern Cooperative Oncology Group performance status 0 or 1 Adequate bone marrow and organ function at baseline Female patients who are women of childbearing potential with confirmed of a negative pregnancy test and agreement to the use of a highly effective contraceptive method or at least 2 effective methods at the same time during study treatment period and for up to 3 months after the last dose of study treatment. Male patients must be willing to use effective barrier contraception during the study treatment period and for up 3 months after the last dose of study treatment. Histologically or cytologically confirmed locally advanced (unresectable) or metastatic solid tumors who meet one of the following criteria (dose escalation only): Relapsed or progressed through standard therapy Have a disease for which no standard effective therapy exists Not a candidate for standard effective therapy Exclusion Criteria: Prior anticancer treatment including: Chemotherapy or small molecule-targeted therapy < 2 weeks prior to first dose of study treatment Any antibody therapy < 5 half-lives from first dose of study treatment (or 4 weeks since last therapy, whichever is the shortest) PD-1 (anti-programmed death 1) or PD-L1 (anti-programmed death ligand 1) therapy < 4 weeks from first dose of study treatment Invasive surgery requiring general anesthesia < 30 days from first dose of study treatment Chemotherapy with nitrosoureas or mitomycin C, < 45 days from first dose of study treatment Radiation therapy (including radiofrequency ablation) < 4 weeks prior to initiation of study treatment Grade 2 or greater toxicity, except alopecia related to any prior treatment (ie, chemotherapy, targeted therapy, radiation, or surgery) Prolongation of QT/QTc interval (QTc interval > 480 msec) using the Frederica method of QTc analysis Women who are pregnant or nursing Seropositive for human immunodeficiency virus (HIV) 1 or 2 or acquired immunodeficiency syndrome (AIDS) or active infection with hepatitis B virus or hepatitis C virus (HCV) Other severe, acute, or chronic medical condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or that may interfere with the interpretation of the study results, and in the judgement of the Investigator, would make the patient inappropriate for the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: KSQ-4279 Monotherapy and KSQ-4279 + Combination (Dose Escalation and Expansion)<br>KSQ-4279 will be administered orally once daily (QD) continuously as monotherapy. Once the maximum tolerated dose (MTD) for KSQ-4279 monotherapy has been reached, KSQ-4279 will be combined in separate cohorts, including combination with an oral PARPi (poly adenosine diphosphate-ribose polymerase inhibitor) and combination with a platinum-based chemotherapy. These cohorts will be enrolled in parallel. | Drug: KSQ-4279 Monotherapy (Dose Escalation and Expansion)<br>* Administered orally in capsule<br>* Other names: USP1 (Ubiquitin Specific Protease 1) inhibitor 4279;Drug: KSQ-4279 Combination Therapy (Dose Escalation and Expansion)<br>* KSQ-4279 will be combined in separate cohorts, including combination with an oral PARPi (poly adenosine diphosphate-ribose polymerase inhibitor) and combination with a platinum-based chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The maximum tolerated dose (MTD) |  | Approximately18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of TEAEs (Treatment Emergent Adverse Events) | Assess safety and tolerability | Approximately 18 months | 
| Overall Response Rate (ORR) per RECIST V1.1 | anti-tumor activity | Approximately18 months |