A Phase 1 Study of RO7623066 Alone and in Combination in Patients with Advanced Solid Tumors

Cancer Categories

Breast,Gastrointestinal (GI),Gynecologic

Karmanos Trial ID

2023-021

NCT ID

NCT05240898

Age Group

Adult

Scope

National

Phase

Phase I

Principal Investigator

Ira
Winer, M.D., Ph.D., FACOG
Oncology - Gynecologic, Oncology - Surgical View Profile

Objective:

Primary Objective:

Determine the maximum tolerated dose
(MTD) and the recommended Phase 2
dose (RP2D) of KSQ-4279 alone and in
combination in patients with advanced
solid tumors

Secondary Objectives:

Assess the safety and tolerability of
KSQ-4279 alone and in combination in
patients with advanced solid tumors
Characterize the PK profile of KSQ-
4279 alone and in combination in
patients with advanced solid tumors
Evaluate preliminary antitumor activity
of KSQ-4279 alone and in combination
in patients with advanced solid tumors

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Eligibility

Inclusion Criteria:

Age 18 years or older
Life expectancy of ≥ 12 weeks
Measurable disease or non-measurable disease per RECIST v1.1 in dose escalation and the Food Effect Cohort only; patients in dose expansion and Backfill Cohorts 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 (ECOG) performance status 0 or 1
Adequate bone marrow function defined as:

absolute neutrophil count of ≥ 1.5 × 109/L
platelet count of ≥ 100.0 × 109/L
hemoglobin of ≥ 10.0 g/dL (with or without transfusion)

Adequate renal function defined as calculated creatinine clearance (Cockcroft- Gault) ≥ 40 mL/min for patients with creatinine levels above institutional normal
Adequate hepatic function defined as:

Total bilirubin ≤ 1.5 × upper limit of normal (ULN) unless associated with Gilbert's syndrome
Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × ULN (or ≤ 5 × ULN in patients with liver metastases)

Female patients who are women of childbearing potential (WOCP) (defined as physiologically and anatomically capable of becoming pregnant), 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 (ie, condoms) during the study treatment period and for up 3 months after the last dose of study treatment
Capable of understanding and complying with protocol requirements
Signed and dated institutional review board (IRB)/independent ethics committee (IEC) approved informed consent form (ICF) before any protocol-directed Screening procedures are performed
Does not require ongoing treatment with strong or moderate CYP3A4 inhibitors or inducers.
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 Note: In men with prostate cancer, baseline testosterone levels must also be ≤ 50 ng/dL (≤ 2.0 nM) and surgical or ongoing medical castration must be maintained throughout the duration of the study

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)
Programmed cell death protein-1 or programmed cell death ligand 1 inhibitor 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 Note: Prior stereotactic body radiation therapy or local palliative radiation is allowed < 2 weeks prior to first dose of study treatment

Ongoing 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 or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) (Note: Patients with positive HCV antibody may be eligible if HCV ribonucleic acid [RNA] is undetectable on a quantitative HCV RNA assay, the Medical Monitor is available for advice)
Primary malignant brain tumor
Symptomatic and/or untreated brain metastases, active leptomeningeal disease, or central nervous system malignant disease requiring steroids or other therapeutic intervention Note: Patients with definitively treated brain metastases will be considered for enrollment after seeking advice from the Medical Monitor and must be clinically stable for ≥ 2 weeks prior to the start of treatment
Previous solid organ or hematopoietic cell transplant
Need for treatment with steroids at stable doses (> 10 mg prednisone or equivalent per day). Note: Oral steroids up to 10 mg/day, topical, ophthalmic, or inhaled steroid medications are allowed
Uncontrolled hypertension > 150/100 mm Hg despite aggressive therapy
Concurrent participation in any other investigational therapeutic study
History of stroke, transient ischemic attack, unstable angina, or myocardial infarction within 3 months prior to first dose of study treatment
Unable to swallow whole tablets or capsules. Nasogastric or gastric-tube (G-tube)administration is not allowed
GI disease that would impair ability to swallow, retain, or absorb drug is not allowed
Uncontrolled concurrent disease or illness including but not limited to:

Symptomatic congestive heart failure according to New York Heart Association (NYHA) classification, Class III or IV (per NYHA Classification) unstable angina pectoris, or clinically significant cardia arrhythmia
Diabetes mellitus (ie, fasting blood glucose > 220 despite acceptable chronic diabetes therapy)
Psychiatric illness that would limit compliance with study requirements, as determined by the Investigator

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 judgment of the Investigator, would make the patient inappropriate for the study
Known hypersensitivity to any component of RO7623066 or excipient
History of and/or ongoing adrenal disorder (eg, Cushing's disease, Addison's disease, adrenal gland suppression)
Suspected pneumonitis or interstitial lung disease (confirmed radiography or by computed tomography [CT]) or a history of pneumonitis or interstitial lung disease in the last 6 months
Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, or other cancer for which the patient has been disease-free for at least 2 years
Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML), or baseline features suggestive of MDS or AML on peripheral blood smear or bone marrow biopsy
Treatment with strong or moderate CYP3A4 inhibitors or inducers for a period of 5 half-lives of the inhibitor or inducer prior to the first dose of RO7623066.

Locations

Karmanos Cancer Institute - Detroit Headquarters

4100 John R
Detroit, MI 48201
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Phone: 800-527-6266

Karmanos Cancer Institute at Weisberg Cancer Center - Farmington Hills

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices