A Study of ABM-1310 in Patients With BRAF V600-Mutant Advanced Solid Tumors

NCT05501912 | Terminated Phase 1 DMC

• 1 other identifier: ABM1310X1101C
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 10

Brief Summary

This is a Phase I, Open-Label, Multicenter, Dose Escalation and Expansion Study to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-cancer activity of ABM-1310 in patients with BRAF V600-Mutant advanced solid tumors. This study consists of two stages: dose escalation and dose expansion. During the dose escalation stage, a classic "3+3" design will be used to guide dose escalation to determine MTD and RP2D. The dose expansion stage will be initiated at the MTD or the optimal dose determined by the Safety Monitoring Committee (SMC ) as a fixed dose level (MTD or the optimal dose needs to be reviewed by the SMC and subjects are safe and tolerable at that dose level).

Conditions

Advanced Solid Tumor; BRAF V600 Mutation

Keywords

Melanoma; Non-small Cell Lung Cancer; Cholangiocarcinoma; intracranial solid tumor

Outcome Measures

Primary Outcomes (11)

• Maximum Tolerated Dose (MTD)

  MTD is defined as the highest dose level at which DLT is observed in ≤ 1/6 subjects at one single dose group

  From the enrollment of subjects to the end of Cycle 1 (each cycle is 28 days) or up to treatment discontinuation, whichever occurs first, assessed up to 33 days.

• Recommended Phase 2 Dose (RP2D)

  RP2D will be a dose either below or equal to MTD

  From the enrollment of subjects to the end of Cycle 1 (each cycle is 28 days) or up to treatment discontinuation, whichever occurs first, assessed up to 33 days.

• Dose Limiting Toxicity (DLT)

  DLT will be evaluated according to NCI-CTCAE V5.0 criteria

  Single dose PK observation period (5 days) and Cycle 1 (28 days) (33 days in total)

• The incidence of treatment-related adverse events AE(s)

  Safety and tolerability of ABM-1310 monotherapy

  Up to 28 days from treatment discontinuation

• Number of participants with abnormal laboratory values

  Safety and tolerability of ABM-1310 monotherapy

  Up to 28 days from treatment discontinuation

• Number of participants with abnormal vital signs

  Safety and tolerability of ABM-1310 monotherapy

  Up to 28 days from treatment discontinuation

• Number of participants with abnormal physical examinations

  Safety and tolerability of ABM-1310 monotherapy

  Up to 28 days from treatment discontinuation

• Number of participants with abnormal ophthalmic evaluation

  Safety and tolerability of ABM-1310 monotherapy

  Up to 28 days from treatment discontinuation

• Number of participants with abnormal ECG

  Safety and tolerability of ABM-1310 monotherapy

  Up to 28 days from treatment discontinuation

• Number of participants with abnormal ECOG

  Safety and tolerability of ABM-1310 monotherapy

  Up to 28 days from treatment discontinuation

• Number of participants with abnormal Karnofsky PS

  Safety and tolerability of ABM-1310 monotherapy

  Up to 28 days from treatment discontinuation

Secondary Outcomes (22)

• Area under the concentration time curve (AUC)

  only 5 days prior to dose escalation stage

• Maximum plasma concentration (Cmax)

  only 5 days prior to dose escalation stage

• Time to maximum plasma concentration (Tmax)

  only 5 days prior to dose escalation stage

• Half-life (T1/2)

  only 5 days prior to dose escalation stage

• Apparent plasma clearance (CL/F)

  only 5 days prior to dose escalation stage

Study Arms (1)

Monotherapy Dose Escalation and Dose Expansion

EXPERIMENTAL

In US studies, dose escalation started at a 25 mg BID dose and subsequent dose-escalation groups included: 50 mg BID, 100 mg BID, 150 mg BID, 225 mg BID and 325 mg BID. In this study, the actual dose escalation will be based on a priming dose one level below the highest safe dose or two levels below the MTD that has been tested in US clinical trials when the enrolment of the China study actually initiates, and subsequent escalated doses may be adjusted as appropriate (e.g., the escalated doses following 150 mg BID in the China study may be adjusted to 200 mg BID, 250 mg BID and 300 mg BID. The actual priming dose and subsequent escalated doses for the China study are determined by the SMC) The dose expansion stage in this study will be initiated at the MTD or the optimal dose determined by the SMC as a fixed dose level (MTD or the optimal dose needs to be reviewed by the SMC and subjects are safe and tolerable at that dose level).

Drug: ABM-1310

Interventions

ABM-1310 DRUG

Dose escalation starting dose will be based on a priming dose one level below the highest safe dose or two levels below the MTD that has been tested in US clinical trials. Dose expansion will be initiated at the MTD or the optimal dose determined by the SMC as a fixed dose level.

Monotherapy Dose Escalation and Dose Expansion

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who are able to understand and voluntarily sign informed consent forms (ICFs).
• Male and female subjects at the age of ≥18 and ≤80 at the time of screening.
• Patients with histologically or cytologically-confirmed, locally advanced, or metastatic solid tumors with (a) failure of prior standard therapy, (b) no standard therapy available, or (c) for whom standard therapy is not applicable considered by the patient or treating physician. There is no limit to the number of prior treatment lines. Subjects who were previously treated with BRAF and/or MEK inhibitors are allowed to be enrolled in this study.
• Documentation of positive BRAF V600 mutation is required for enrollment (the blood BRAF V600 test report is received at the dose-escalation stage). Representative tumor specimens suitable for confirmation of BRAF V600 mutations by retrospective analysis are required (for dose-expansion stage only). It is recommended to provide sufficient fresh/archived tumor tissue samples (formalin-fixed paraffin-embedded tumor specimens \[preferred\]) or 5-10 available unstained sections of good quality for verification of BRAF V600 mutation status at the central laboratory. For any subject who is unable to provide suitable and adequate tumor specimens, re-biopsy (with controllable safety) can be performed in a non-mandatory manner if it is feasible as assessed by the investigator and the subject gives informed consent; if re-biopsy is impossible or refused by the subject, his/her eligibility for enrollment shall be confirmed by both the investigator and the sponsor.
• Patients with BMs/primary intracranial solid tumors that are asymptomatic, or that are symptomatic but on a stable or decreasing dose of steroids for at least 2 weeks are eligible for enrollment. The specific criteria are as follows:
• Subjects with inactive and asymptomatic BMs/primary intracranial solid tumors;
• Subjects who have active, mild neurological signs and symptoms currently requiring no therapy with steroids, and have no history of epileptic seizure within 2 weeks prior to initiation of treatment;
• Subjects who have active, neurological signs and symptoms and were on a stable or gradually reducing dose up to 4 mg of dexamethasone (or equivalent) per day within 2 weeks prior to initiation of treatment;
• Subjects who only have evaluable lesions are allowed to be included for the dose escalation stage. They must have at least one measurable lesion (intracranial or extracranial) as defined by RECIST V1.1 criteria or modified RECIST v1.1 for subjects with BMs or the RANO criteria for subjects with primary intracranial solid tumors during screening at the dose expansion stage. Lesions previously treated with radiotherapy shall not be deemed as target lesions unless significant progression as shown on imaging.
• o For BMs from solid tumors;At least one measurable extracranial lesion is required if the longest diameter of the intracranial lesion is less than 0.5 cm (for dose expansion stage only).Subjects with measurable intracranial lesions of 0.5-3 cm in longest diameter (the lower limit of the longest diameter is defined according to the modified RECIST V1.1 criteria are allowed for the study, and measurable extracranial lesions are not required.Subjects with intracranial lesions \> 3 cm in longest diameter are not eligible for the study.
• ECOG score of 0 or 1 or Karnofsky PS score of ≥ 70.
• Life expectancy \> 3 months.
• Adequate organ function (no blood transfusion and no use of granulocyte colony-stimulating factor, or other hematopoietic stimulator support within 2 weeks before the first administration of the study drug) confirmed as evidenced by:
• Absolute Neutrophil Count (ANC) ≥ 1.5×10\^9/L;
• Hemoglobin (Hgb) ≥ 90 g/dl;

You may not qualify if:

• Women who are pregnant or breast-feeding.
• Subjects with intracranial hypertension or associated risks (e.g., intracranial infection, intracranial hemorrhage).
• Subjects with clinically uncontrolled pleural effusion, pericardial effusion, or ascites who, in the judgement of the investigator, are not eligible for enrollment.
• Subjects with cancerous meningitis (leptomeningeal disease \[LMD\]).
• Subjects with history of symptomatic stroke within 6 months prior to initiation of study treatment.
• Subjects with epileptic seizure within 14 days prior to initiation of study treatment.
• Impaired cardiac function or clinically significant cardiovascular disorder, including but not limited to any of the following:
• Left Ventricular Ejection Fraction (LVEF) \< 50% as determined via cardiac ultrasound.
• Long QT syndrome congenital.
• QTcF (as corrected via Fridericia formula) ≥ 450 ms (males) or 470 ms (females) at screening.
• Second-degree type II AV block or third-degree AV block.
• Unstable angina pectoris within 6 months prior to starting study drug.
• Acute myocardial infarction within 6 months prior to starting study drug.
• New York Heart Association (NYHA) Class II or higher heart failure within 6 months prior to study treatment.
• Ventricular arrhythmias \> Grade 2 within 6 months prior to study treatment.

Sponsors & Collaborators

• ABM Therapeutics Shanghai Company Limited: lead

Study Sites (10)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Beijing Tsinghua Changgeng Hospital

Beijing, Beijing Municipality, 102218, China

Location

Xuzhou Medical University Affiliated Hospital

Xuzhou, Jiangsu, 221006, China

Location

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330200, China

Location

Jilin Cancer Hospital

Changchun, Jilin, 130012, China

Location

Affiliated Cancer Hospital of Shandong First Medical University (Shandong Cancer Institute, Shandong Cancer Hospital)

Jinan, Shandong, 250117, China

Location

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200030, China

Location

Zhongshan Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

Huashan Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, 200040, China

Location

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200120, China

Location

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Related Links

• CNKI References

MeSH Terms

Conditions

Melanoma; Carcinoma, Non-Small-Cell Lung; Cholangiocarcinoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial

Study Officials

• Jin Li, M.D.

  Shanghai East Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will be conducted in two stages: Dose escalation stage: To determine MTD/RP2D and evaluate the safety and tolerability of ABM-1310 monotherapy. Dose expansion stage: To further determine RP2D and evaluate the preliminary efficacy of ABM-1310 monotherapy.

Study Record Dates

• First Submitted: August 11, 2022
• First Posted: August 16, 2022
• Study Start: September 1, 2022
• Primary Completion: June 17, 2024
• Study Completion: June 17, 2024
• Last Updated: November 29, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (10)