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

• ClinicalTrials.gov Identifier: NCT05240898
• Recruitment Status: Recruiting
• First Posted: February 15, 2022
• Last Update Posted: April 6, 2022
• Sponsor: KSQ Therapeutics, Inc.
• Information provided by (Responsible Party): KSQ Therapeutics, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumors	Drug: KSQ-4279; Drug: KSQ-4279 will be combined in separate cohorts, including combination with an oral PARPi (poly adenosine diphosphate-ribose polymerase inhibitor)	Phase 1

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 140 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of KSQ-4279 Alone and in Combination in Patients With Advanced Solid Tumors
• Actual Study Start Date: August 16, 2021
• Estimated Primary Completion Date: December 19, 2023
• Estimated Study Completion Date: October 15, 2024

Arms and Interventions

Arm

Intervention/treatment

Experimental: KSQ-4279 Monotherapy and KSQ-4279 + Combination (Dose Escalation and Expansion); 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). These cohorts will be enrolled in parallel.

Drug: KSQ-4279; Administered orally in capsule; Other Name: USP1 (Ubiquitin Specific Protease 1) inhibitor 4279; Drug: KSQ-4279 will be combined in separate cohorts, including combination with an oral PARPi (poly adenosine diphosphate-ribose polymerase inhibitor); KSQ-4279 will be combined in separate cohorts, including combination with an oral PARPi (poly adenosine diphosphate-ribose polymerase inhibitor)

Outcome Measures

Primary Outcome Measures :

1. The maximum tolerated dose (MTD) [ Time Frame: Approximately18 months ]

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Maximum observed concentration (Cmax) [ Time Frame: Predose and up to 12 hours postdose. ]
   Measure the maximum observed concentration for KSQ-4279 alone and in combination
2. Time to maximum observed concentration (Tmax) [ Time Frame: Predose and up to 12 hours postdose. ]
   Measure time to maximum observed concentration for KSQ-4279 alone and in combination
3. Minimum observed concentration (Cmin) [ Time Frame: Predose and up to 12 hours postdose ]
   Measure time to Minimum observed concentration for KSQ-4279 alone and in combination
4. Area under the concentration-time curve( AUC) [ Time Frame: Predose and up to 12 hours postdose. ]
   Measure area under the concentration-time curve for KSQ-4279 alone and in combination

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age 18 years or older
2. Life expectancy of ≥ 12 weeks
3. 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
4. Recovered to ≤ Grade 1 or baseline toxicity (except alopecia) from prior therapy (per NCI-CTCAE v5.0)
5. Eastern Cooperative Oncology Group performance status 0 or 1
6. Adequate bone marrow and organ function at baseline
7. 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.

8. Histologically or cytologically confirmed locally advanced (unresectable) or metastatic solid tumors who meet one of the following criteria (dose escalation only):

   1. Relapsed or progressed through standard therapy
   2. Have a disease for which no standard effective therapy exists
   3. Not a candidate for standard effective therapy

Exclusion Criteria:

1. Prior anticancer treatment including:

   1. Chemotherapy or small molecule-targeted therapy < 2 weeks prior to first dose of study treatment
   2. Any antibody therapy < 5 half-lives from first dose of study treatment (or 4 weeks since last therapy, whichever is the shortest)
   3. PD-1 (anti-programmed death 1) or PD-L1 (anti-programmed death ligand 1) therapy < 4 weeks from first dose of study treatment
   4. Invasive surgery requiring general anesthesia < 30 days from first dose of study treatment
   5. Chemotherapy with nitrosoureas or mitomycin C, < 45 days from first dose of study treatment
   6. Radiation therapy (including radiofrequency ablation) < 4 weeks prior to initiation of study treatment
2. Grade 2 or greater toxicity, except alopecia related to any prior treatment (ie, chemotherapy, targeted therapy, radiation, or surgery)
3. Prolongation of QT/QTc interval (QTc interval > 480 msec) using the Frederica method of QTc analysis
4. Women who are pregnant or nursing
5. 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)
6. 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

Contacts and Locations

Contacts

Contact: Patricia Harris; 617-674-9187; pharris@ksqtx.com

Contact: Brigid Garelik; 617-674-9187; bgarelik@ksqtx.com

Locations

United States, Massachusetts

Boston, Massachusetts; Recruiting

Boston, Massachusetts, United States, 02115

United States, Michigan

Grand Rapids, Michigan; Recruiting

Grand Rapids, Michigan, United States, 49546-7062

United States, New Jersey

Hackensack, NJ; Recruiting

Hackensack, New Jersey, United States, 07601

United States, Texas

Houston, TX; Recruiting

Houston, Texas, United States, 77030-4000

San Antonio,TX; Recruiting

San Antonio, Texas, United States, 78229-3307

Sponsors and Collaborators

KSQ Therapeutics, Inc.

Investigators

• Study Director: Brigid Garelik; KSQ Therapeutics, Inc.

More Information

• Responsible Party: KSQ Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT05240898
• Other Study ID Numbers: KSQ-4279-1101
• First Posted: February 15, 2022
• Last Update Posted: April 6, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasms; Adenosine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Vasodilator Agents; Purinergic P1 Receptor Agonists; Purinergic Agonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action