A Study of MAX-40279combined With KN046 in Patients With Advanced / Metastatic Solid Tumors

A I / II Clinical Study to Evaluate the Safety, Tolerance, Pharmacokinetic Characteristics and Efficacy of MAX-40279 (Multi-target Tyrosine Kinase Inhibitor) Combined With KN046 (Anti-PD-L1 / CTLA-4 Bispecific Antibody) in Patients With Advanced / Metastatic Solid Tumors

This include two parts, Stage 1 is a dose climbing study and Stage 2 is a dose extending study.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced / Metastatic Solid Tumors
• Intervention / Treatment: Drug: MAX-40279-01: 50mg/70mg

Detailed Description

This study is a study of MAX-40279 in patients with advanced / metastatic solid tumors. This study include two Parts, the Part 1 will assess the safety and efficacy of the dose climbing level of MAX-40279, and recommend a dose extending level of MAX-40279 for stage 2.

• Study Type: Interventional
• Enrollment (Anticipated): 108
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Ting Peng, MD,Ph.D; Phone Number: 13917659695; Email: tpeng@maxinovel.com
• Study Contact Backup: Name: Zhengbo Song, MD,Ph.D; Phone Number: 0571-88122168; Email: songzb@zjcc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed informed consent form.
2. Males and/or females over age 18 and 75.
3. Histologically or cytologically documented local advanced / metastatic solid tumors who have failed standard treatment or cannot obtain standard treatment in the dose escalation stage; dose expansion stage group A: relapsed and refractory advanced gastric cancer; dose expansion stage group B: relapsed and refractory extensive stage small cell lung cancer; dose expansion stage group C: other relapsed and refractory solid tumors except group A
4. At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
6. Expected survival of more than 3 months.

Exclusion Criteria:

1. The adverse reactions of previous anti-tumor treatment have not recovered to CTCAE 5.0 grade evaluation ≤ 1 (except alopecia and other adverse reactions without safety risks judged by the investigator)
2. Subject is known to have previous serious allergic reactions to macromolecular protein preparations/monoclonal antibodies, or known to any component of the test drug
3. Active systemic infectious diseases requiring intravenous antibiotic treatment 2 months before the first medication
4. Subject has poorly controlled cardiovascular and cerebrovascular clinical symptoms or diseases, including but not limited to: such as: (1) NYHA class II or higher heart failure or LVEF < 50%; (2) unstable angina pectoris; (3) myocardial infarction and cerebral infarction within 6 months; (4) clinically significant supraventricular or ventricular arrhythmias are still poorly controlled without clinical intervention or clinical intervention
5. brain metastases, spinal cord compression, carcinomatous meningitis with clinical symptoms, or other evidence of uncontrolled brain and spinal cord metastases, Patients who are not suitable by the investigator's judgment
6. Patients who have experienced ≥ grade 3 immune-related adverse events in immunotherapy (except grade 3 hypothyroidism that can be controlled by drugs)
7. Patients who have other malignant tumors within 5 years before enrollment,Exceptions: a. radical cervical carcinoma in situ or non-melanoma skin cancer; b. radical second primary cancer without recurrence within five years; c. the investigator believes that the double primary cancer can benefit from this study; d. the investigator has clearly excluded which primary tumor source the metastasis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: MAX40279-01+KN046; This is an open-label Phase I/II clinical study. Drug: Stage1: Dose1:MAX40279-01 (35mg BID)+KN046 ( 5mg/kg Q3Week) Drug: Stage1: Dose2:MAX40279-01( 50mg BID)+KN046 ( 5mg/kg Q3Week) Drug: Stage1: Dose3:MAX40279-01( 70mg BID)+KN046 ( 5mg/kg Q3Week) Drug: Stage2: Dose3:MAX40279-01( RP2D BID)+KN046 ( 5mg/kg Q3Week)

Drug: MAX-40279-01: 50mg/70mg; [Stage 1]The starting dose of MAX-40279 was 35 mg BID, and three dose levels were initially set: 35 mg, 50 mg, and 70 mg administered twice daily (BID) continuously, and the dose of KN046 was 5 mg/kg as a fixed dose administered every 3 weeks. [Stage 2]When the RP2D dose is obtained in the dose-finding phase, the trial will enter the dose expansion phase.; Other Names: KN046: 40mg/300mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
DLT	through study Stage1 completion，an average of 6 months
Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D)	through study Stage1 completion，an average of 6 months
ORR	through study Stage2 completion，an average of 24 months
PFS	through study Stage2 completion，an average of 24 months
Adverse events (AEs), serious adverse events (SAEs)	through study Stage2 completion，an average of 24 months
laboratory tests	through study Stage2 completion，an average of 24 months
vital signs	through study Stage2 completion，an average of 24 months
12 ECG	through study Stage2 completion，an average of 24 months
physical examination abnormalities	through study Stage2 completion，an average of 24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events (AEs), serious adverse events (SAEs)	through study Stage1 completion，an average of 6 months
Cmax	through study Stage1 completion，an average of 6 months
Anti-KN046 antibody (ADA	through study Stage1 completion，an average of 6 months
Duration of response (DOR) Overall survival (OS); Anti-KN046 antibody (ADA); Plasma concentrations of MAX-40279 and KN046 [Stage 2]	through study Stage2 completion，an average of 24 months
(AUC0-t and AUC0-t, ss)	through study Stage1 completion，an average of 6 months
Tmax	through study Stage1 completion，an average of 6 months
Overall response rate (ORR)	through study Stage1 completion，an average of 6 months
disease control rate (DCR)	through study Stage1 completion，an average of 6 months
duration of response (DOR)	through study Stage1 completion，an average of 6 months
progression-free survival (PFS)	through study Stage1 completion，an average of 6 months
overall survival (OS)	through study Stage1 completion，an average of 6 months
DcR	through study Stage2 completion，an average of 24 months
DoR	through study Stage2 completion，an average of 24 months
OS	through study Stage2 completion，an average of 24 months
Anti-KN046 antibody (ADA)	through study Stage2 completion，an average of 24 months
Rac (AUC0-t, ss/AUC0-t)	through study Stage1 completion，an average of 6 months
laboratory tests	through study Stage1 completion，an average of 6 months
vital signs	through study Stage1 completion，an average of 6 months
12 ECG	through study Stage1 completion，an average of 6 months
physical examination abnormalities	through study Stage1 completion，an average of 6 months

Other Outcome Measures

Outcome Measure	Time Frame
FGFR1OP2-related protein expression levels and mutations, PD-L1 and related inflammatory factors correlate with efficacy [Stage 1]	through study Stage1 completion，an average of 6 months
FGFR1OP2-related protein expression levels and correlation of mutations, PD-L1, tumor mutation burden, and related inflammatory factors with efficacy.[ Stage 2]	through study Stage2 completion，an average of 24 months

Collaborators and Investigators

• Sponsor: Maxinovel Pty., Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 31, 2022
• Primary Completion (Anticipated): December 30, 2023
• Study Completion (Anticipated): December 30, 2024

Study Registration Dates

• First Submitted: April 18, 2022
• First Submitted That Met QC Criteria: June 16, 2022
• First Posted (Actual): June 21, 2022

Study Record Updates

• Last Update Posted (Actual): June 21, 2022
• Last Update Submitted That Met QC Criteria: June 16, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: MAX-40279-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No