A Study of PM1015 in Patients With Advanced Solid Tumors

NCT05950815 | Unknown Phase 1

• 1 other identifier: PM1015-A001M-ST-R
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

PM1015 is a specific antibody targeting CD73. This is a phase I study to evaluate the efficacy and safety of PM1015 in patients with advanced solid tumor.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Dose Limited Toxicity (DLT)

  Occurrence of DLT after receiving PM1009 injection

  up to 21 days

• Treatment-related adverse events (TRAEs)

  The incidence and severity of TRAEs graded according to NCI-CTCAE v5.0

  Up to 30 days after last treatment

Secondary Outcomes (12)

• Objective response rate (ORR)

  Up to 24 months

• Disease control rate (DCR)

  Up to 24 months

• Progression-free survival (PFS)

  Up to 24 months

• Overall survival (OS)

  Up to 24 months

• Anti-drug antibody (ADA)

  Up to 30 days after last treatment

Study Arms (1)

PM1015

EXPERIMENTAL

Subjects will be administered PM1015 via intravenously (IV) once in first cycle, then administered PM1015 every 2 weeks (Q2W ) after 3 weeks

Drug: CD73 Antigen

Interventions

CD73 Antigen DRUG

subjects will be administered with PM1015 via intravenously (IV) Q2W pemetrexed until progression or accepted other treatment.

Also known as: PM1015 injection

PM1015

Eligibility Criteria

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

You may qualify if:

• Volunteer to participate in clinical trials; Fully understand the test and voluntarily sign the informed consent; Willing to follow and able to complete all test procedures;
• No gender limit, aged between 18 and 75 years (including boundary values);
• Subjects with histologically or cytologically confirmed advanced malignant solid tumors who have failed standard treatment, have no standard treatment options, or are not currently eligible for standard treatment;
• Adequate organ function, as defined below:
• Blood system (in the absence of blood transfusion, granulocyte colony stimulating factor, or other medical support within 14 days prior to initiation of trial therapy) : neutrophil count (ANC) \>= 1.5 x 10\^9 /L; Platelet count (PLT) \>= 100 x 10\^9 /L; Hemoglobin (Hb) \>= 90 g/L;
• Liver function: total bilirubin (TBIL) \<= 1.5 x upper limit of normal (ULN), subjects with liver metastasis or liver cancer \<= 2 x ULN; Subjects with Gilbert disease should be \<= 3 x ULN; Aspartate aminotransferase (AST), alanine aminotransferase (ALT) \<= 2.5 x ULN (subjects with liver metastasis or liver cancer: \<= 3 x ULN);
• Renal function: serum creatinine \<= 1.5 x ULN or creatinine clearance \>= 50 mL/min (Cockcroft-Gault formula: \[(140 - age) x body weight (kg) x 0.85 (for females only)\] / \[72 x creatinine (mg/dL)\]; (Creatinine unit conversion: 1 mg/dL = 88.4 μmol/L); Qualitative urine protein \<= 1+; If the qualitative urine protein \>= 2+, 24h urine protein quantitative examination is required; if the quantitative urine protein \< 1g, it is acceptable;
• Coagulation function: International standardized ratio (INR) and activated partial thrombin time (APTT) should be less than 1.5 x ULN; Subjects with liver metastasis or liver cancer should be \<= 2 x ULN;
• Physical status: The Eastern Cooperative Oncology Group (ECOG) physical status score was 0-1;
• Expected survival \>= 12 weeks;
• Dose escalation test: According to RECIST version 1.1, there is at least one evaluable tumor lesion; Initial dose extension test: At least one measurable tumor lesion according to RECIST version 1.1; (Tumor lesions located in the area of previous radiotherapy or other local regional treatment sites are generally not considered as measurable lesions, unless the lesions show definite progression or persist 3 months after radiotherapy; Not accept only bone metastases or only central nervous system metastases as measurable lesions);
• All subjects should undergo a fresh tumor lesion biopsy during the screening period (No bone biopsy; Biopsy is also not acceptable in subjects with a single target lesion for biopsy); If biopsy is not possible, subjects should provide formalin-fixed-paraffin-embedded (FFPE) tumor samples from the nearest (up to 24 months) to the start of the trial for biomarker analysis; If the subject is unable to provide specimens that meet the above requirements due to special reasons, the subject may participate in screening with the consent of the sponsor's medical monitor;
• A fertile female subject has a negative serum-pregnancy result within 7 days prior to the start of the trial treatment and is willing to abstain from sex or use a medically approved highly effective contraceptive method (e.g. IUD, condom) from the date of signing the informed consent to 6 months after the end of the final medication;
• Male subjects are willing to abstain from sex or use a medically approved highly effective contraceptive method for 6 months from the date of signing the informed consent, and do not donate sperm during this period.

You may not qualify if:

• History of severe allergic disease, allergy to serious drugs (including unmarketed test drugs) or known allergy to any component of the test drug;
• Previous treatment with adenosine inhibitors (such as anti-CD73, anti-CD39, or anti-A2aR);
• Received an unmarketed investigational drug or treatment within 4 weeks prior to initiation of the trial treatment, or is still within the drug's 5 half-lives (if known), whichever is longer;
• The adverse reactions of previous antitumor therapy have not recovered to the NCI-CTCAE V5.0 rating \<= grade 1 (except for toxicities without safety risks as determined by the researchers, such as hair loss, grade 2 peripheral neurotoxicity, stable hypothyroidism after hormone replacement therapy, etc.);
• Received the following treatments or drugs before starting the trial therapy:
• Major organ surgery (excluding needle biopsy) or major trauma or invasive dental procedures within 4 weeks before the initiation of trial treatment, or the need for elective surgery during the trial;
• Within 4 weeks prior to initiation of trial therapy, received chemotherapy, radical/extensive radiotherapy, endocrine therapy, biological therapy (such as tumor vaccine, cytokine), immune checkpoint agonists (such as 4-1BB agonists, OX40 agonists) or immune checkpoint inhibitors (such as anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-LAG-3) and other anti-tumor therapy; Received nitrosourea and mitomycin C within 6 weeks prior to initiation of treatment; Received oral fluorouracil, small-molecule targeted drugs, and traditional Chinese medicine with anti-tumor indications within 2 weeks before the start of the experimental treatment; Received palliative radiotherapy for vital organs (such as liver, brain, lung, etc.) within 7 days prior to the start of trial therapy;
• Received systemic glucocorticoid (prednisone \>10 mg/ day or equivalent dose of the same drug) or other immunosuppressant therapy within 14 days prior to the initial use of the test drug; Except in the following cases: treatment with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; Short-term use of glucocorticoids for preventive treatment (e.g. to prevent hypersensitivity to contrast media);
• Have received live attenuated vaccine within 4 weeks before the first use of the trial drug;
• History of immune deficiency, including HIV antibody positive test;
• Syphilis antibody positive;
• Active infection;
• Subjects with active or previous autoimmune diseases with potential recurrence (e.g. systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except clinically stable autoimmune thyroid disease and type I diabetes;
• Currently with uncontrollable pleural, pericardial and abdominal effusion;
• A history of severe cardiovascular and cerebrovascular diseases, including but not limited to:

Sponsors & Collaborators

• Biotheus Inc.: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, China

RECRUITING

MeSH Terms

Interventions

5'-Nucleotidase

Intervention Hierarchy (Ancestors)

Nucleotidases; Phosphoric Monoester Hydrolases; Esterases; Hydrolases; Enzymes; Enzymes and Coenzymes

Study Officials

• Lin Shen, PhD

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhishuo Cheng

CONTACT

+86 199 1072 4988; cheng.zs@biotheus.com

Study Design

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

Study Record Dates

• First Submitted: May 18, 2023
• First Posted: July 18, 2023
• Study Start: May 10, 2022
• Primary Completion: September 30, 2023
• Study Completion: September 30, 2024
• Last Updated: July 18, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: After the trial completed
• Access Criteria: NCI is committed to sharing data in accordance with NIH policy.

Locations

CN (1)