Clinical trial NCT05764915: A Phase I Study of RGT-264 in Subjects With Advanced Solid Tumors
Official title: A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of RGT-264 Phosphate Tablets in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: Hematopoietic progenitor kinase 1 (HPK1)
Dose Escalation
Dose Expansion
RGT-264
First-in-Human
Lead sponsor: Regor Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2023-03-13
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: There will be one arm in the study. Enrolled subjects will be treated with RGT-264 phosphate tablets alone.
Primary purpose: TREATMENT

Brief summary: This is a Phase 1 dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of RGT-264 as monotherapy in subjects with advanced solid tumors.

Detailed description: This first-in-human (FIH) study of RGT-264 will evaluate safety, pharmacokinetics (PK) and efficacy of RGT-264 in subjects with advanced solid tumors. The primary objective is to determine the maximum tolerated dose (MTD)/maximum administered dose (MAD) and the recommended phase II dose (RP2D) of RGT-264 as monotherapy, and to evaluate the safety and tolerability of RGT-264. The secondary objectives include the assessments of PK profile and preliminary efficacy of RGT-264.

Eligibility criteria: Inclusion Criteria:

* Able to sign the ICF and agree to comply with the requirements of the study;
* Subjects with pathologically confirmed advanced solid tumors who have failed standard-of-care therapy, or have no standard-of-care therapy available, or are currently not eligible for standard-of-care therapy;
* ECOG performance status score of 0 to 1;
* Expected survival ≥ 3 months;
* With at least one measurable lesion per RECIST v1.1;
* Subjects should discontinue all anti-tumor therapies prior to receiving study treatment, and the toxicity caused by prior anti-tumor therapy has recovered to ≤ Grade 1 per CTCAE v5.0;
* The specific requirements of washout period should be met before first dose;
* Adequate organ function
* Female subjects of childbearing potential must have a negative pregnancy test prior to the first dose and are required to use effective contraception from signing the ICF until 6 months after the last dose of study treatment

Exclusion Criteria:

* Presence of risks that may significantly affect the absorption of the investigational product (e.g. inability to swallow, intestinal obstruction, chronic diarrhea, etc.);
* Having received immunotherapy and experienced ≥ Grade 3 immune-related adverse events (irAEs) or ≥ Grade 2 immune-related myocarditis;
* Having received systemic glucocorticoids (\> 10 mg/day of prednisone or equivalent) or other immunosuppressants within 14 days prior to the first dose of investigational product;
* Presence of symptomatic parenchymal brain metastasis or leptomeningeal metastasis;
* Active, or previous autoimmune disease with the potential for relapse (excluding well-controlled type 1 diabetes mellitus; manageable hypothyroidism with hormone replacement therapy only).;
* Any other malignancy (except cured basal cell carcinoma of skin and in-situ carcinoma of the cervix) within 3 years prior to the first dose;
* History of serious cardiovascular and cerebrovascular diseases;
* Presence of active interstitial lung disease or history of interstitial lung disease requiring glucocorticoid treatment;
* Presence of severe chronic or active infections (including tuberculosis infection, etc.) requiring intravenous antimicrobial, antifungal or antiviral therapy;
* Active HBV or HCV infection;
* History of immunodeficiency or organ transplantation;
* Presence of uncontrolled third spacing fluid;
* Concomitant diseases or any other conditions that may seriously jeopardize the subject's safety or affect the subject's completion of the study, at the discretion of the investigator.

Primary outcomes:
measure: Number of subjects with Dose-Limiting Toxicities (DLTs) at each cohort dose level in dose escalation stage
timeFrame: Day 1 to Day 21 after first dose (21 days)
measure: Number of subjects with adverse events (AEs)
timeFrame: From screening (Day -28 to Day -1) through up to 12 months or until disease progression
Secondary outcomes:
measure: Pharmacokinetic Assessments: Time to maximum plasma concentration (Tmax)
timeFrame: PK Blood (Cycle 1 Day 1 and Cycle 1 Day 15; PK Urine (Cycle 1 Day 1) (each cycle is 21 days)
measure: Pharmacokinetic Assessments: Maximum concentration (Cmax)
timeFrame: PK Blood (Cycle 1 Day 1 and Cycle 1 Day 15; PK Urine (Cycle 1 Day 1) (each cycle is 21 days)
measure: Pharmacokinetic Assessments: Elimination half-life (t1/2)
timeFrame: PK Blood (Cycle 1 Day 1 and Cycle 1 Day 15; PK Urine (Cycle 1 Day 1) (each cycle is 21 days)
measure: Pharmacokinetic Assessments: Area under the concentration-time curve over time 0 to t (AUC0-t)
timeFrame: PK Blood (Cycle 1 Day 1 and Cycle 1 Day 15; PK Urine (Cycle 1 Day 1) (each cycle is 21 days)
measure: Pharmacokinetic Assessments: Area under the concentration-time curve over time 0 to infinite (AUC0-inf)
timeFrame: PK Blood (Cycle 1 Day 1 and Cycle 1 Day 15; PK Urine (Cycle 1 Day 1) (each cycle is 21 days)
measure: Pharmacokinetic Assessments: Accumulation ratio (Rac)
timeFrame: PK Blood (Cycle 1 Day 1 and Cycle 1 Day 15; PK Urine (Cycle 1 Day 1) (each cycle is 21 days)
measure: Pharmacokinetic Assessments: Cumulative urinary excretion
timeFrame: Cycle 1 Day 1 (each cycle is 21 days)
measure: Tumor Response
timeFrame: Screening until disease progression, initiation of a new anti-tumor therapy, death, loss to follow-up, withdrawal of consent, or meeting other end-of-study criteria (whichever occurs first) (Assessed up to 12 months).
Other outcomes:
Locations:
city: Nanchang
country: China
facility: The First Affiliated Hospital Of Nanchang University City
state: Jiangxi
city: Jinan
country: China
facility: Shandong Provincial Institute of Cancer Prevention and Treatment
state: Shandong
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
Study officials:
References: