The dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses.

first dose: 2.5mg QD, n=1;

The dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses.

second dose: 5mg QD, n=3;

The dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses.

third dose: 10mg QD, n=3;

The dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses.

fourth dose: 20mg, n=3;

The dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses.

fifth dose: 30mg, n=3;

The dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses.

sixth dose: 40mg, n=9;

The dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses.

seventh dose: 60mg, n=15;

The subjects in each dose level will be administered single oral dose of LM-061 tablet on C0D1, and washout for 5 days. After that, the subjects will be administered multiple oral doses once daily (QD) in continuous 28 days (4 weeks) per treatment cycle, until meet the treatment termination criteria, including disease progression or unaccepted toxicity, etc. After obtaining MTD/RP2D, the Safety Review Committee (SRC) may combine the data of safety, PK, and preliminary efficacy to explore other dosing schedules (such as 3 weeks on and 1 week off).

LM-061

This is a phase I/II, open-label, dose escalation and dose extension study to evaluate the safety, tolerability, PK, and preliminary efficacy of LM-061 in subjects with advanced tumors.

This is a phase I/II, open-label, dose escalation and dose extension study to evaluate the safety, tolerability, PK, and preliminary efficacy of LM-061 in subjects with advanced tumors.

The study schedule includes screening visit (28 days prior to accept the investigational medicinal product (IMP)), treatment visit (accept IMP for the first time to the end of treatment (EOT)/early withdrawal), and follow-up visit (28 days after the EOT/early withdrawal).

Arm1: LM-061 2.5mg P.O QD Arm2: LM-061 5mg, P.O QD Arm3: LM-061 10mg, P.O QD Arm4: LM-061 20mg, P.O QD Arm5: LM-061 30mg, P.O QD Arm6: LM-061 40mg, P.O QD Arm7: LM-061 60mg, P.O QD

A Clinical Study Preliminary Efficacy of LM-061 Tablet in Subjects With Advanced Tumours

A Phase I/II, First-in-Human, Open-Label, Dose-Escalation and Dose-Extension Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of LM-061 Tablet in Subjects With Advanced Tumours

The safety profile of LM061 will be assessed by monitoring the adverse events (AE) per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

DLT is defined as a toxicity (adverse event at least possibly related to LM061) occurring during the DLT observation period (the initial 21 days)

MTD is defined as the dose for which the probability of DLT does not exceed the upper bound of the EI, 0.35, and is closest to the target toxicity probability p_T=0.3 during the DLT assessment period (from LM-061 single dose to the first treatment cycle of the multiple dose).

The i3+3 design does not select a dose as the MTD unless at least 3 subjects have completed the safety assessment.

Change in vital signs-ear temperature will be measured after the subject has been fully rested.

Change in vital signs-pulse rate will be measured after the subject has been fully rested.

Change in vital signs-blood pressure will be measured after the subject has been fully rested.

RR interval of 12-lead ECG will be performed in the supine position after the patients are fully rested at each timepoint for once. RR is the standard heart rate which calculated by 60 divided by heart rate.

QT interval of 12-lead ECG will be performed in the supine position after the patients are fully rested at each timepoint for once.

QRS duration of 12-lead ECG will be performed in the supine position after the patients are fully rested at each timepoint for once.

Number of participants with incidence of abnormal clinical lab test results like hematology will be assessed.

Number of participants with incidence of abnormal clinical lab test results like Biochemistry will be assessed.

Number of participants with incidence of abnormal clinical lab test results like Urinalysis will be assessed.

Number of participants with incidence of abnormal clinical lab test results like Coagulation test will be assessed.

To determine the pharmacokinetics (PK) profile of LM061 Single dose: pre-dose (within 30 minutes before administration), and 1 h, 3 h, 6 h, 8 h, 10 h, 12 h, 24 h, 36 h, 48 h, 72 h, 96 h after administration on C0D1; Multiple dose: pre-dose (within 30 minutes before administration) on C1D1, C1D8, and C1D15; pre-dose (within 30 minutes before administration), and 1 h, 3 h, 6 h, 8 h, 10 h, 12 h, 24 h after administration on C1D22;

The timepoints of PK sample may be adjusted base on the human PK data. The blood samples for PK analysis will be collected as much as possible if the subjects end of treatment/early withdraw.

To determine the pharmacokinetics (PK) profile of LM061 For AML, the efficacy will be evaluated by using the European LeukemiaNet (ELN) 2017 criteria. The complete blood count and bone marrow will be evaluated at screening visit and every 4 weeks ± 1 week (relative to C1D1) after the start of multiple administrations until the progressive disease judged by investigator or initiate new anti-tumour therapy or subject withdraw. The assessment results are divided into complete remission (CR), CR without minimal residual disease (CRMRD-)，CR with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MFLS), partial remission (PR), stable disease (SD), progressive disease (PD).

To determine the pharmacokinetics (PK) profile of LM061

To assess the preliminary antitumor activity of LM102,The ORR, using RECIST 1.1 criteria, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) at any time during the study, based on Investigator assessment.

To assess the preliminary antitumor activity of LM061

LaNova Medicines Limited

Antineoplastic Agents

All Drugs and Chemicals

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Olaparib is available as a film-coated tablet containing 150 mg or 100 mg of olaparib. Subjects will be administered study treatment orally at a dose recommended by Investigator. Full dose: 300 mg twice daily (bid) or Reduced doses: 200 mg twice daily (bid) or 100 mg twice daily (bid). The planned dose of 300 mg bid will be made up of two x 150 mg tablets twice daily, with 100 mg tablets used to manage dose reductions.

olaparib

Jane Robertson, BSc, MBCHB, MD

Bella Kaufman, MD

To assess the efficacy of oral olaparib in patients with advanced cancer who have a confirmed genetic BRCA1 and/or BRCA2 mutation, by assessment of tumour response

Open Label Study to Assess Efficacy and Safety of Olaparib in Confirmed Genetic BRCA1 or BRCA2 Mutation Pats

A Phase II, Open Label, Non Randomised, Non Comparative, Multicentre Study to Assess the Efficacy and Safety of Olaparib Given Orally Twice Daily in Patients With Advanced Cancers Who Have a Confirmed Genetic BRCA 1 and/or BRCA2 Mutation

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Tumour response rate is the proportion of patients who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1).

Objective response rate is the proportion of patients with at least one measurable lesion at baseline, who experienced complete or partial response at least once during the assessment period, according to the definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1).

Progression free survival is defined as the duration from first dose till objective progression or death. In absence of progression or death, the time is calculated from first dose till last evaluable scanning visit.

Overall survival is defined as the duration from first dose till death. In absence of death, the time is calculated from first dose till the date subject last known to be alive.

Overall survival rate at 12 months is defined as the proportion of patients who are alive 12 months after date of first dose

Duration of response is calculated from the date of first documented response (complete or partial) until date of documented progression (as defined by RECIST 1.1) or death (by any cause) in the absence of disease progression.

Disease control rate is the proportion of patients with best response of complete or partial response or stable disease according to definitions of Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) till week 16.

AstraZeneca

OLAPARIB

Patients with primary cancer site = breast. Receiving olaparib 400mg BID

Breast Cancer

Patients with primary cancer site = ovary. Receiving olaparib 400mg BID

Ovarian Cancer

Patients with primary cancer site = pancreas. Receiving olaparib 400mg BID

Pancreatic Cancer

Patients with primary cancer site = prostate. Receiving olaparib 400mg BID

Prostate Cancer

Patients with other primary cancers. Receiving olaparib 400mg BID

Other Cancers

Total

Age, Continuous

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

Anitra Fielding

All Patients

Tumour Response Rate

Measurable disease analysis set - all treated patients having at least one measurable lesion at baseline

Objective Response Rate

Full analysis set - all treated patients. The Other cancer group was not analysed in accordance with the protocol.

Progression Free Survival

Overall Survival

Overall Survival Rate at 12 Months

Full analysis set - all treated patients who had at least one complete or partial response during the assessment period.

Duration of Response

Disease Control Rate at Week 16

Overall Study

The dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses. The subject in single agent dose levels will be administered multiple oral doses of LM-061 once daily.

The dose escalation scheme using the the accelerated titration design for dose 1 and the i3+3 design for the remaining doses. The subjects in combination dose levels will be administered multiple oral doses once daily of LM-061 and Toripalimab fixed dose injections every 3 weeks

Oral dose with approximately 240 mL water in the fasting condition, and food will be forbidden 1 h prior to administration and 2h after dose. QD for continuous 28 days, and 4 weeks as one treatment cycle.

For subjects in combination escalation levels, toripalimab will be administered 240mg, IV, every 3 weeks

Toripalimab

Vinod Ganju

Ganessan Kichenadasse

Paul De Souza

Gary Richardson

This is a phase I, open-label, dose escalation study to evaluate the safety, tolerability, PK, and preliminary efficacy of LM-061 in subjects with advanced tumors.

This is a phase I, open-label, dose escalation study to evaluate the safety, tolerability, PK, and preliminary efficacy of LM-061 in subjects with advanced tumors.

The study schedule includes screening visit (28 days prior to accept the investigational medicinal product (IMP)), treatment visit (accept IMP for the first time to the end of treatment (EOT)/early withdrawal), and follow-up visit (28 days after the EOT/early withdrawal).

Arm1: LM-061 single agent escalation Arm2: LM-061 combination escalation

Study of LM-061 in Subjects in Advanced Tumors

A Phase I, First-in-Human, Open-Label, Dose Escalation Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of LM-061 Tablet in Subjects With Advanced Tumors

Change in vital signs-pluse rate will be measured after the subject has been fully rested.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Clinical Study Preliminary Efficacy of LM-061 Tablet in Subjects With Advanced Tumours	NCT04882176	Advanced Tumour...	LM-061	18 Years - 75 Years	LaNova Medicines Limited
Open Label Study to Assess Efficacy and Safety of Olaparib in Confirmed Genetic BRCA1 or BRCA2 Mutation Pats	NCT01078662	Ovarian Breast Prostate Pancreatic Advanced Tumour...	olaparib	18 Years - 130 Years	AstraZeneca
Study of LM-061 in Subjects in Advanced Tumors	NCT04737122	Advanced Tumour...	LM-061 Toripalimab	18 Years - 75 Years	LaNova Medicines Limited
Study of LM-061 in Subjects in Advanced Tumors	NCT04737122	Advanced Tumour...	LM-061 Toripalimab	18 Years - 75 Years	LaNova Medicines Limited
Study of LM-061 in Subjects in Advanced Tumors	NCT04737122	Advanced Tumour...	LM-061 Toripalimab	18 Years - 75 Years	LaNova Medicines Limited
Open Label Study to Assess Efficacy and Safety of Olaparib in Confirmed Genetic BRCA1 or BRCA2 Mutation Pats	NCT01078662	Ovarian Breast Prostate Pancreatic Advanced Tumour...	olaparib	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for advanced tumours