Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

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Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Sotorasib

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Subjects with locally advanced or metastatic KRAS G12C-mutated NSCLC refractory to or relapsed on prior KRASG12C inhibitor therapy will receive VIC-1911 monotherapy.

Subjects with locally advanced or metastatic KRAS G12C-mutated NSCLC refractory to or relapsed on prior KRASG12C inhibitor therapy or are naive to KRAS G12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy.

Subjects with locally advanced or metastatic KRAS G12C-mutated NSCLC refractory to or relapsed on prior KRASG12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy.

Subjects with locally advanced or metastatic KRAS G12C-mutated NSCLC naive to KRAS G12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy.

VIC-1911

Sotorasib tablets for oral administration

sotorasib

Sarah Goldberg, MD, MPH

Linda J Paradiso, DVM

This is a Phase 1a/1b study of aurora kinase A inhibitor VIC-1911 administered as monotherapy and in combination with sotorasib for the treatment of locally advanced or metastatic KRAS G12C-mutant non-small cell lung cancer(NSCLC).

Selected subjects will include males and females age ≥18 years; histologically confirmed locally advanced or metastatic KRAS G12C-mutated NSCLC; received at least 1 prior line of cancer therapy with a PD-1 or PD-L1 inhibitor with or without platinum-based chemotherapy; recovered from all acute toxicities (≤ Grade 1) due to prior therapy; adequate renal and hepatic function; and no known history of significant cardiac, hepatic or ocular disease.

Dose Escalation Phase:

Following screening, a total of up to 36 subjects are anticipated to establish the dose limiting toxicity (DLT) and maximum tolerated doses (MTDs) of VIC-1911 monotherapy and VIC-1911 in combination with sotorasib therapy.

Cohort 1a: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will receive VIC-1911 monotherapy. Up to 24 subjects are anticipated in this cohort.

Cohort 1b: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy or are naïve to KRASG12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy. Up to 12 subjects are anticipated in this cohort.

A 3+3 dose escalation schema will be followed to establish the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of VIC-1911 and VIC-1911 plus sotorasib combination. A total of at least 6 subjects will be treated at the MTD in each group before initiating the Expansion Phase.

Expansion Phase:

Following screening, a total of 104 subjects with KRAS G12C-mutated locally advanced or metastatic NSCLC are anticipated to expand the disease treatment settings of VIC-1911 as monotherapy or in combination with sotorasib. VIC-1911 monotherapy and VIC-1911 plus sotorasib combination therapy will be administered orally at the MTDs established during the Dose Escalation Phase.

Cohort 2a: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will receive VIC-1911 monotherapy. (n=29)

Cohort 2b: Subjects who are refractory to or relapsed on prior KRAS G12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy.(n=29)

Cohort 2c: Subjects who are naïve to KRAS G12C inhibitor therapy will receive VIC-1911 plus sotorasib combination therapy. (n=46)

VIC-1911 and sotorasib will be taken in the fasted state, 1 hour before or 2 hours after a meal.

Subjects who demonstrate clinical benefit (CR, PR or SD) will be allowed to continue therapy with VIC-1911 and sotorasib until progression of disease, observation of unacceptable adverse events, intercurrent illness or changes in the subject's condition that prevents further study participation.

Disease response will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST v.1.1).

Blood for hematology, coagulation parameters and serum chemistry determinations and urine will be collected, ECGs will be taken and ophthalmologic exams will be conducted during the study.

Blood will be taken for PK assessment of VIC-1911 and PD assessment of circulating tumor DNA biomarker determinations.

Tumor biopsies will be taken from consenting subjects at Screening and on-study for correlative biomarker determinations. Results will be correlated with clinical outcome.

Dose Escalation Phase followed by Expansion Phase. A total of 24 subjects are anticipated in Dose Escalation Phase, Cohort 1a. A total of 12 subjects are anticipated in Dose Escalation Phase, Cohort 1b. A total of 29 subjects are anticipated in Expansion Phase, Cohort 2a. A total of 29 subjects are anticipated in Expansion Phase, Cohort 2b. A total of 46 subjects are anticipated in Expansion Phase, Cohort 2c.

VIC-1911 Monotherapy in Combination With Sotorasib for the Treatment of KRAS G12C-Mutant Non-Small Cell Lung Cancer

A Phase 1a/1b Study of Aurora Kinase A Inhibitor VIC-1911 Monotherapy and in Combination With Sotorasib for the Treatment of KRAS G12C-Mutant Non-Small Cell Lung Cancer

Mean plasma concentrations of VIC-1911 will be determined and summarized by dose group.

Changes from baseline will be determined, summarized by dose group and correlated with clinical outcome

The effect of prior KRAS G12C de novo resistance (KRAS G12C inhibitor treatment ≤ 3 months) versus KRAS G12C acquired resistance (KRAS G12C inhibitor treatment \> 3 months) on clinical outcome

Safety and tolerability assessed by adverse events(AEs) and serious adverse events (SAEs)

Proportion of subjects with objective responses (complete response \[CR\] + partial response \[PR\]) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1.

Length of time from first evidence of objective response (CR, PR) to the first objective evidence of disease progression

Length of time from the date of first dose of study drug to the first evidence of objective response (CR,PR)

Proportion of subjects with best response of CR, PR or stable disease (SD)

Length of time from the date of first dose of study drug to the first evidence of disease progression or death, whichever is earlier

Length of time from the date of first dose of study drug to date of death from any cause

Westat

Vitrac Therapeutics, LLC

Subjects with advanced solid tumors will be enrolled in dose escalation cohorts. Dose escalation of HS-10370 will be done to determine maximum tolerated dose.

Depending on data obtained from the dose escalation part, dose expansion may proceed with multiple cohorts in subjects with advanced solid tumors having a KRAS G12C mutation.

Subjects with locally advanced or metastatic KRAS G12C mutant NSCLC will be enrolled in phase 2 part to evaluate the efficacy and sufficient safety of HS-10370 as monotherapy.

HS-10370 will be administered orally once daily in a continuous regimen

HS-10370

Xiaorong Dong, PhD

HS-10370 is an oral, highly selective, small molecular inhibitor of KRAS G12C. This study will evaluate the safety, tolerability, pharmacokinetics and clinical activity of HS-10370 in Chinese advanced solid tumor patients.

This is a phase 1/2, first-in-human, open-label, multicenter study of HS-10370, this study has two parts: phase 1 and phase 2. The phase 1 portion consists of dose escalation and dose expansion, which is aimed to assess the safety and tolerability of HS-10370 in subjects with advanced solid tumors and evaluate the preliminary efficacy of HS-10370. Phase 2 will be conducted to evaluate the efficacy of HS-10370 in subjects with locally advanced or metastatic NSCLC with a KRAS G12C mutation.

Phase 1/2 Study of HS-10370 in Patients With Advanced Solid Tumors

A Phase 1/2, Open-label, Multicenter Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-10370 Monotherapy in Patients With Advanced Solid Tumors

Number of participants with dose limiting toxicity

Objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)

Number of participants with treatment related adverse events.

In the study of single-dose, Cmax will be obtained following administration of a single oral dose of HS-10370 on Day 1 to Day 6

In the study of single-dose, Tmax will be obtained following administration of a single oral dose of HS-10370 on Day 1 to Day 6.

Apparent terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.

Jiangsu Hansoh Pharmaceutical Co., Ltd.

BEBT-607 tablets, 100mg/day,50mg each time, are administered once a day in the single administration phase and twice a day in the continuous administration phase (only once on the 28th day of the first cycle) for 28 days. 28 days is as a treatment cycle.

BEBT-607 tablets, 200mg/day,100mg each time, are administered once a day in the single administration phase and twice a day in the continuous administration phase (only once on the 28th day of the first cycle) for 28 days. 28 days is as a treatment cycle.

BEBT-607 tablets, 300mg/day,150mg each time, are administered once a day in the single administration phase and twice a day in the continuous administration phase (only once on the 28th day of the first cycle) for 28 days. 28 days is as a treatment cycle.

BEBT-607 tablets, 400mg/day,200mg each time, are administered once a day in the single administration phase and twice a day in the continuous administration phase (only once on the 28th day of the first cycle) for 28 days. 28 days is as a treatment cycle.

BEBT-607 tablets, 600mg/day,300mg each time, are administered once a day in the single administration phase and twice a day in the continuous administration phase (only once on the 28th day of the first cycle) for 28 days. 28 days is as a treatment cycle.

BEBT-607 tablets, 800mg/day,400mg each time, are administered once a day in the single administration phase and twice a day in the continuous administration phase (only once on the 28th day of the first cycle) for 28 days. 28 days is as a treatment cycle.

BEBT-607 tablets, 300mg/day,150mg each time, are administered twice a day (only once on day 1 and day 28 of the first cycle), continuous administration for 28 days. 28 days is as a treatment cycle.

BEBT-607 tablets, 400mg/day,200mg each time, are administered twice a day (only once on day 1 and day 28 of the first cycle), continuous administration for 28 days. 28 days is as a treatment cycle.

BEBT-607 tablets, 600mg/day,300mg each time, are administered twice a day (only once on day 1 and day 28 of the first cycle), continuous administration for 28 days. 28 days is as a treatment cycle.

PhaseⅠa:100mg,200mg,300mg,400mg,600mg or 800mg/day,50mg,100mg,150mg,200mg,300mg or 400mg each time, once a day in the single administration phase and twice a day in the continuous administration phase (only once on the 28th day of the first cycle) for 28 days,28 days is as a treatment cycle.

PhaseⅠb:300mg,400mg or 600mg/day, 150mg,200mg or 300mg each time,twice a day (only once on day 1 and day 28 of the first cycle), continuous administration for 28 days,28 days is as a treatment cycle.

BEBT-607Tablets

Kegang Jiang, Master

Heli Liu, Ph.D

Zhenhua Liu

This is a two-phase, multicenter, open phase I clinical study, with phase Ia as dose escalation phase and phase Ib as dose expansion phase, to evaluate the safety tolerability and pharmacokinetic characteristics of BEBT-607 tablets in patients with advanced or metastatic solid tumors associated with KRAS G12C mutation. To evaluate the efficacy of BEBT-607 tablets in the treatment of patients with advanced or metastatic solid tumors with KRAS G12C mutation, and to determine the recommended dose (RP2D) for Phase II clinical trials of BEBT-607 tablets in patients with advanced or metastatic solid tumors with KRAS G12C mutation.

Phase Ⅰa:

The dose escalation plan is to carry out about 6 dose levels. The initial dose of BEBT-607 tablets is set at 100mg/ day, and the subsequent dose groups are first increased by 100%. If a case of drug-related grade 2 non-hematological toxicity or grade 3 hematological toxicity is found and does not reach DLT, the subsequent dose groups are increased by 50%. If one case of dose limiting toxicity(DLT) is found and does not reach maximum tolerated dose(MTD ), the subsequent dose group is increased by 33%（Doses are rounded to multiples of 100mg）.The single dose is 1/2 of the total daily dose, and the single administration phase is administered once a day, and the continuous administration phase is administered twice a day (only once on the 28th day of the first cycle).

Phase Ⅰb:

According to the pharmacokinetics, safety and preliminary efficacy results of phase Ⅰa dose escalation phase, one to three cohorts with target dose or tumor species are selected for dose extension trial, and a maximum of 30 subjects are enrolled in each cohort. The subjects receive BEBT-607 tablets twice a day, orally before breakfast and before dinner, respectively. There is a treatment cycle every 28 days (On days 1 and 28 of the first cycle, the drug is administered only once before breakfast). The study process for each subject consisted of three phases: screening, treatment, and follow-up. During treatment, participants are required to undergo safety checks every four weeks from the first dose, tumor assessments every eight weeks, safety follow-up at the end of treatment 28 days after the last dose, efficacy follow-up every eight weeks, and survival follow-up every three months.

Participants will need to understand the requirements and risks of the trial, sign an informed consent form, accept the dosing regimen required by the trial protocol, and follow the investigator's guidance.

Phase Ⅰa:

Six dose levels are carried out, and the initial dose of BEBT-607 tablets is set as 100mg/ day. The climbing study is carried out by accelerated titration method combined with "3+3" mode.

Phase Ⅰb:

According to the pharmacokinetics, safety, and preliminary efficacy results of phase Ⅰa , one to three cohorts with target dose or tumor species are selected for dose extension trial, in which participants receive continuous administration of the experimental drug BEBT-607 tablets until disease progression or toxicity became intolerable or patients stopped or died.

Study of BEBT-607 Tablets in The Treatment of Advanced or Metastatic Solid Tumors With KRAS G12C Mutation

A Two-phase, Multicenter, Open Phase I Study of BEBT-607 Tablets in The Treatment of Advanced or Metastatic Solid Tumors With KRAS G12C Mutation

Area under the plasma concentration time curve from 0 hour to last time of quantifiable concentration after administration

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
VIC-1911 Monotherapy in Combination With Sotorasib for the Treatment of KRAS G12C-Mutant Non-Small Cell Lung Cancer	NCT05374538	Non-small Cell ...	VIC-1911 sotorasib	18 Years -	Vitrac Therapeutics, LLC
VIC-1911 Monotherapy in Combination With Sotorasib for the Treatment of KRAS G12C-Mutant Non-Small Cell Lung Cancer	NCT05374538	Non-small Cell ...	VIC-1911 sotorasib	18 Years -	Vitrac Therapeutics, LLC
Phase 1/2 Study of HS-10370 in Patients With Advanced Solid Tumors	NCT05367778	Advanced Solid ...	HS-10370	18 Years -	Jiangsu Hansoh Pharmaceutical Co., Ltd.
Study of BEBT-607 Tablets in The Treatment of Advanced or Metastatic Solid Tumors With KRAS G12C Mutation	NCT06117371	Advanced or Met... KRAS G12C Mutat...	BEBT-607Tablets	18 Years -	BeBetter Med Inc

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