Study of LM-102 in Patients With Advance Solid Tumors

NCT05008445 | Terminated Phase 1

• 1 other identifier: LM102-01-102
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label Phase I/II trial of LM-102 injection, a recombinant humanized monoclonal antibody targeting Claudin 18.2 (CLDN18.2). It is being tested in advanced solid tumors including gastric cancer/gastroesophageal junction adenocarcinoma, Pancreatic Cancer, Biliary Tract Cancer, esophageal adenocarcinoma and ovarian mucous carcinoma.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (4)

• The incidence and case number of DLT (Dose Limiting Toxicity) during observation period

  DLT is short for Dose Limiting Toxicity. dose-limiting describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment.

  up to 21 days following first dose

• Participant Safety as characterized by frequency and severity of adverse events(according to NCI CTCAE 5.0)

  An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

  up to 31 days following last dose or other anti-cancer therapy

• Recommended Phase II Dose (RP2D)

  The RP2D will be determined during the dose expansion stage of the study. RP2D will be determined using available safety and efficacy data.

  up to 21 days following first dose

• Maximum Tolerated Dose (MTD）

  The MTD is defined as the dose of which the toxicity rate is lower than the upper bound of EI p\_T+ϵ\_1= 0.35 and closest to the target toxicity rate of p\_T= 0.3 during the DLT observation period (21 days after the first administration in cycle 1 on day 1).

  up to 21 days following first dose

Secondary Outcomes (8)

• Area under plasma concentration vs time curve (AUC) for LM-102

  Up to finished circle 5 (each cycle is 21 days)

• Peak plasma concentration (Cmax) for LM-102

  Up to finished circle 5 (each cycle is 21 days)

• Time to maximum observed plasma concentration (Tmax)

  Up to finished circle 5 (each cycle is 21 days)

• Terminal elimination half life (t1/2)

  Up to finished circle 5 (each cycle is 21 days)

• Immunogenicity

  up to 31 days following last dose

Study Arms (7)

LM-102 Dose Escalation Level 1, 3mg/kg

EXPERIMENTAL

The dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses. first dose: 3mg/kg, Q3W;

Biological: LM-102 Injection

LM-102 Dose Escalation Level 2, 10mg/kg

EXPERIMENTAL

The dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses. Second dose: 10mg/kg, Q3W;

Biological: LM-102 Injection

LM-102 Dose Escalation Level 3, 20mg/kg

EXPERIMENTAL

The dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses. Third dose: 20mg/kg, Q3W;

Biological: LM-102 Injection

LM-102 Dose Escalation Level 4, 30mg/kg

EXPERIMENTAL

The dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses. Four dose: 30mg/kg, Q3W;

Biological: LM-102 Injection

LM-102 Dose Escalation Level 5, 40mg/kg

EXPERIMENTAL

The dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses. Five dose: 40mg/kg, Q3W;

Biological: LM-102 Injection

LM-102 (RP2D-1) combined with SOC Dose Escalation

EXPERIMENTAL

During the dose escalation of LM-102 combined with SOC,the next lower dose groups (RP2D-1) of LM-102 monotherapy's RP2D will be adopted as the starting dose.

Combination Product: LM-102 Injection combined with SOC

LM-102 (RP2D) combined with SOC Dose Escalation

EXPERIMENTAL

During the dose escalation of LM-102 combined with SOC,(If applicable) LM-102 monotherapy's RP2D will be adopted as the starting dose.

Combination Product: LM-102 Injection combined with SOC

Interventions

LM-102 Injection BIOLOGICAL

LM-102 Injection with dose escalation stage of 3mg/kg up to 40mg/kg, as well as dose expansion stage with recommended dose level from dose escalation stage.

LM-102 Dose Escalation Level 1, 3mg/kg; LM-102 Dose Escalation Level 2, 10mg/kg; LM-102 Dose Escalation Level 3, 20mg/kg; LM-102 Dose Escalation Level 4, 30mg/kg; LM-102 Dose Escalation Level 5, 40mg/kg

LM-102 Injection combined with SOC COMBINATION_PRODUCT

LM-102 Injection with appropriate dose level(s), combined with SOC.

LM-102 (RP2D) combined with SOC Dose Escalation; LM-102 (RP2D-1) combined with SOC Dose Escalation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who are fully informed of the purpose, nature, method and possible adverse reactions of the study, and are willing to participate in the study and sign the informed consent document prior to any procedure;
• Aged between 18 to 75 years old, male or female when sign the Informed consent form (ICF);
• Subjects who meet the criteria:
• Phase I dose escalation:
• Part Ia: Subjects have histological or cytological confirmation of recurrent or refractory advanced solid tumors, and are intolerable for available standard therapy, or there is no available standard therapy.
• Part Ib:Subjects have been histologically or cytologically confirmed advanced solid tumors and meet the criteria as follows: No previous systemic chemotherapy was given for the recurrent or metastatic disease or for the subjects who have received curative treatment (including neo-adjuvant or adjuvant chemotherapy /radiotherapy, etc.), the interval between recurrence and the last dose of previous anti-cancer treatment must be more than 6 months.
• Phase II dose expansion: subjects with positive CLDN18.2 confirmed by central immunohistochemistry (IHC).
• Part IIa: Subjects have histological or cytological confirmation of recurrent or refractory advanced solid tumors, and are intolerable for available standard therapy, or there is no available standard therapy.
• Part IIb: Subjects have histological or cytological confirmation of advanced solid tumors and meet the criteria as follows: No previous systemic chemotherapy was given for the recurrent or metastatic disease, or for the subjects who have received curative treatment (including neo-adjuvant or adjuvant chemotherapy /radiotherapy, etc.), the interval between recurrence and the last dose of previous anti-cancer treatment must be more than 6 months;
• At least one evaluable lesion for phase I and one measurable lesion for phase II according to RECIST v1.1;
• ECOG score 0-1;
• Life expectancy ≥ 3 months;
• Subjects must have the following organ and marrow function in laboratory tests within 7 days prior to the first dose;
• Subjects who are able to well communicate with investigators as well as understand and adhere to the requirements of this study.

You may not qualify if:

• Subjects will be excluded from the study, if they meet any of the following criteria:
• Child-bearing potential female who have positive results in pregnancy test or are lactating;
• Subjects who known to be allergic to the similar products or any of its excipients;
• Exposure to any IMP, or participate in any other clinical trial within 21 days prior to 1st dosing of LM-102;
• Subjects with anti-tumor treatment within 28 days prior to 1st dosing of LM-302, including radiotherapy, chemotherapy, biotherapy, endocrine therapy and immunotherapy, etc.
• Subjects who have received surgical or interventional treatment within 28 days prior to 1st dosing LM-102, with the exception for tumor biopsy, puncture, etc.;
• Subjects who have received the treatment targeting to CLDN18.2 or ADCs;
• Use of any live vaccines (e.g., against infectious diseases such as influenza, varicella etc.) within 28 days prior to 1st dosing of LM-102;
• Subjects with the history of interstitial lung disease or drug-induced interstitial lung disease/pneumonitis;
• Subjects who are taking therapeutic doses of anticoagulants such as heparin or vitamin K antagonists (except for preventive treatment at a stable dose);
• Subjects with gastric outlet obstruction, persistent recurrent vomiting or uncontrolled/severe gastrointestinal hemorrhage, or ulcer within 28 days prior to 1st dosing;
• Subjects who are unable to take the oral drugs, have the conditions that severely affect gastrointestinal absorption;
• Subjects with known central nervous system (CNS) or meningeal metastasis;
• Subjects who have uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures;
• Subjects who have severe cardiovascular disease;

Sponsors & Collaborators

• LaNova Medicines Development Co., Ltd.: lead
• Shanghai Zhongshan Hospital: collaborator
• First Affiliated Hospital of Harbin Medical University: collaborator
• First Affiliated Hospital of Zhejiang University: collaborator
• Sir Run Run Shaw Hospital: collaborator

Study Sites (1)

Fudan Zhongshan Hospital

Shanghai, Shanghai Municipality, Xuhui District, China

Location

Study Officials

• Tianshu Liu

  Shanghai Zhongshan Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2021
• First Posted: August 17, 2021
• Study Start: October 6, 2021
• Primary Completion: February 8, 2023
• Study Completion: February 28, 2023
• Last Updated: March 9, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)