Study of LaNova Medicines(LM)-302 in Combination With Toripalimab in Patients With Advanced Solid Tumors

NCT05188664 | Completed Phase 1 DMC

• 1 other identifier: LM302-01-201
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase I/II, Open-Label, Multiple Centre Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Preliminary Efficacy of LM- 302 in Combination with Toripalimab in Patients with Advanced Solid Tumors

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (4)

• DLT

  To assess the safety and tolerability for LM-302 in combination with toripalimab in subjects with advanced solid tumors.

  Cycle 1 of each cohort. Duration of one cycle is 21 days

• RP2D

  Obtain the recommended phase 2 dose (RP2D) for LM-302 in combination with toripalimab in subjects with advanced solid tumors.

  Up to 6 months

• OBD

  Obtain the optimal biologic dose (OBD) for LM-302 in combination with toripalimab in subjects with advanced solid tumors.

  Up to 6 months

• MTD

  Obtain the Maximum Tolerated Dose (MTD) for LM-302 in combination with toripalimab in subjects with advanced solid tumors.

  Up to 21 days

Study Arms (3)

LM-302 monotherapy dose escalation

EXPERIMENTAL

LM-302 monotherapy dose escalation (part Ia). Accelerated titration combined with traditional 3+3 design will be used for monotherapy dose escalation (part Ia).

Drug: LM-302

LM-302 in combination therapy dose escalation

EXPERIMENTAL

LM-302 in combination therapy dose escalation (part Ib).Accelerated titration combined with traditional 3+3 design will be used for LM-302 in combination with fixed dose Toripalimab dose escalation (part Ib).

Drug: LM-302; Drug: Toripalimab

LM-302 Dose Expansion

EXPERIMENTAL

SMC will select appropriate dose(s) and/or tumor types for dose expansion study.

Drug: LM-302; Drug: Toripalimab

Interventions

LM-302 DRUG

LM-302 is given by intravenous (IV) infusion on day 1 every 3 weeks。

LM-302 Dose Expansion; LM-302 in combination therapy dose escalation; LM-302 monotherapy dose escalation

Toripalimab DRUG

Toripalimab with a fixed dose is given by intravenous (IV) infusion on day 1 every 3 weeks.

Also known as: Tuoyi

LM-302 Dose Expansion; LM-302 in combination therapy dose escalation

Eligibility Criteria

• Age: 18 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 form (ICF) prior to any procedure.
• Aged ≥18 years old when sign the ICF, male or female.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and no deterioration within 2 weeks prior to the first dose.
• Life expectancy ≥ 3 months.
• Subjects must have histological or cytological confirmation of recurrent or refractory advanced solid tumors, and have progressed on standard therapy, or are intolerable for available standard therapy, or there is no available standard therapy.
• CLDN18.2 test should be performed for the enrolled subjects if the archived tumor tissue samples are available.
• At least one measurable lesion for phase II dose expansion, according to RECIST v1.1 as assessed by the investigator.
• Subjects must show appropriate organ and marrow function in laboratory examinations within 7 days prior to the first dose:
• Bone marrow reserve: Platelet count (PLT) ≥ 90 × 109/L; Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Haemoglobin ≥ 9 g/dL, without receiving EPO, G-CSF, or GM-CSF within 14 days and blood transfusion including red blood cell and platelet transfusion in at least 7 days prior to first dose.
• Coagulation function: INR ≤ 1.5; APTT ≤ 1.5 × ULN.
• Liver function: Total bilirubin ≤ 1.5 × ULN (Subjects with Gilbert's Syndrome are allowed if total bilirubin ≤ 3 × ULN); AST and ALT ≤ 2.5 × ULN without liver metastases (≤ 5 × ULN if liver metastases are present); Albumin ≥ 2.5 g/dL.
• Kidney function: Serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 50 mL/min.
• Cardiac function: Left ventricular ejection fraction (LVEF) ≥ 50%; QT interval (QTcF) ≤ 480 ms.
• Subjects who are able to communicate well with investigators and understand and adhere to the requirements of this study.

You may not qualify if:

• Participate in any other clinical trial within 28 days prior to 1st dosing of investigational medicinal product (IMP).
• Subjects with anti-tumor treatment within 21 days prior to 1st dosing of IMP, including radiotherapy, chemotherapy, biotherapy, endocrine therapy and immunotherapy, etc. the following treatments have different time limits:
• Local small-scale palliative radiotherapy (bone metastasis radiotherapy to control pain) within 14 days prior to 1st dosing.
• Oral anti-tumor therapy, including fluorouracil antitumor drugs and small molecular targeted drugs, etc. within 14 days or 5 half-lives of the drug (whichever is longer) prior to 1st dosing.
• Traditional herbal medicine with anti-tumor indication within 14 days prior to 1st dosing.
• Nitrosourea or Mitomycin C within 42 days prior to 1st dosing.
• Subjects who experienced grade 3 or higher hypersensitivity to the treatment that contains monoclonal antibody, e.g., monoclonal antibody therapy, ADC etc.
• Subjects who were intolerable to the treatment with MMAE based ADCs or anti-CLDN18.2 antibodies, but they can be enrolled if they were tolerable to the treatments and have experienced a 28-day's washout period prior to 1st dosing of IMP.
• Subjects who were intolerable to the immunotherapy targeting PD-1 receptor, or its ligand PD-L1.
• Any adverse event from prior anti-tumor therapy has not yet recovered to ≤ grade 1 of CTCAE v5.0.
• Administrate strong inhibitors/strong inducers of CYP3A4 within 14 days prior to 1st dosing of IMP.
• Subjects who take systemic corticosteroids (\> 10 mg daily prednisone equivalents) or other systemic immunosuppressive medications.
• Pre-existing peripheral sensory or motor neuropathy ≥ Grade 2.
• Subjects with uncontrolled pain. Subjects requiring analgesic treatment must be on a stable regimen before participating in the study.
• Subjects with known central nervous system (CNS) or meningeal metastasis.

Sponsors & Collaborators

• LaNova Australia Pty Limited: lead

Study Sites (1)

The Alfred

Melbourne, Australia

Location

MeSH Terms

Interventions

toripalimab

Study Officials

• Vinod Ganju

  Peninsula & South Eastern Haematology and Oncology Group

  PRINCIPAL INVESTIGATOR

• Ben Markman

  The Alfred

  PRINCIPAL INVESTIGATOR

• Sophia Frentzas

  Monash Medical Centre Clayton

  PRINCIPAL INVESTIGATOR

• Sara Wahlroos

  Chris O'Brien Lifehouse

  PRINCIPAL INVESTIGATOR

• Jessica Smith

  Macquarie University

  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

Model Details: This study includes two stages, Phase I (Dose escalation) which includes LM-302 monotherapy dose escalation (part Ia) and LM-302 in combination with Toripalimab therapy dose escalation (part Ib) and Phase II (Dose expansion).

Study Record Dates

• First Submitted: December 8, 2021
• First Posted: January 12, 2022
• Study Start: May 10, 2022
• Primary Completion: November 14, 2023
• Study Completion: November 14, 2023
• Last Updated: February 17, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)