Clinical trial NCT05425602: A Study of MAX-40279combined With KN046 in Patients With Advanced / Metastatic Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Advanced / Metastatic Solid Tumors
Lead sponsor: Maxinovel Pty., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-06-21
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: DLT
timeFrame: through study Stage1 completion，an average of 6 months
measure: Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D)
timeFrame: through study Stage1 completion，an average of 6 months
measure: ORR
timeFrame: through study Stage2 completion，an average of 24 months
measure: PFS
timeFrame: through study Stage2 completion，an average of 24 months
measure: Adverse events (AEs), serious adverse events (SAEs)
timeFrame: through study Stage2 completion，an average of 24 months
measure: laboratory tests
timeFrame: through study Stage2 completion，an average of 24 months
measure: vital signs
timeFrame: through study Stage2 completion，an average of 24 months
measure: 12 ECG
timeFrame: through study Stage2 completion，an average of 24 months
measure: physical examination abnormalities
timeFrame: through study Stage2 completion，an average of 24 months
Secondary outcomes:
measure: Adverse events (AEs), serious adverse events (SAEs)
timeFrame: through study Stage1 completion，an average of 6 months
measure: Cmax
timeFrame: through study Stage1 completion，an average of 6 months
measure: Anti-KN046 antibody (ADA
timeFrame: through study Stage1 completion，an average of 6 months
measure: Duration of response (DOR) Overall survival (OS); Anti-KN046 antibody (ADA); Plasma concentrations of MAX-40279 and KN046 [Stage 2]
timeFrame: through study Stage2 completion，an average of 24 months
measure: (AUC0-t and AUC0-t, ss)
timeFrame: through study Stage1 completion，an average of 6 months
measure: Tmax
timeFrame: through study Stage1 completion，an average of 6 months
measure: Overall response rate (ORR)
timeFrame: through study Stage1 completion，an average of 6 months
measure: disease control rate (DCR)
timeFrame: through study Stage1 completion，an average of 6 months
measure: duration of response (DOR)
timeFrame: through study Stage1 completion，an average of 6 months
measure: progression-free survival (PFS)
timeFrame: through study Stage1 completion，an average of 6 months
measure: overall survival (OS)
timeFrame: through study Stage1 completion，an average of 6 months
measure: DcR
timeFrame: through study Stage2 completion，an average of 24 months
measure: DoR
timeFrame: through study Stage2 completion，an average of 24 months
measure: OS
timeFrame: through study Stage2 completion，an average of 24 months
measure: Anti-KN046 antibody (ADA)
timeFrame: through study Stage2 completion，an average of 24 months
measure: Rac (AUC0-t, ss/AUC0-t)
timeFrame: through study Stage1 completion，an average of 6 months
measure: laboratory tests
timeFrame: through study Stage1 completion，an average of 6 months
measure: vital signs
timeFrame: through study Stage1 completion，an average of 6 months
measure: 12 ECG
timeFrame: through study Stage1 completion，an average of 6 months
measure: physical examination abnormalities
timeFrame: through study Stage1 completion，an average of 6 months
Other outcomes:
measure: FGFR1OP2-related protein expression levels and mutations, PD-L1 and related inflammatory factors correlate with efficacy [Stage 1]
timeFrame: through study Stage1 completion，an average of 6 months
measure: FGFR1OP2-related protein expression levels and correlation of mutations, PD-L1, tumor mutation burden, and related inflammatory factors with efficacy.[ Stage 2]
timeFrame: through study Stage2 completion，an average of 24 months
Locations:
Study officials:
References: