A Study of PM1021 (Anti-TIGIT) With or Without PM8001 (Anti-PD-L1/TGF-β) in Patients With Advanced Solid Tumours

NCT05537051 | Unknown Phase 1 DMC

• 1 other identifier: PM10218001-A001C-ST-R
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this research is to assess the safety, tolerability and effectiveness of PM1021 Monotherapy and PM1021 in Combination with PM8001 in Patients with Advanced Solid Tumours. In this study, up to 30 patients will be enrolled in Australia only. Advanced solid cancers are associated with poor prognosis and pose a significant challenge for treatment strategies. Effective treatments for advanced metastatic malignancies that have failed available standard of care treatment represent a major unmet medical need. Biotheus Inc. is developing PM1021, a monoclonal anti-T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) antibody (IgG1) and PM8001 (a PD-L1/TGF-beta bispecific Fc fusion protein) as treatment for advanced solid tumours.

Conditions

Advanced Solid Tumours

Keywords

PM1021; PM8001; monotherapy; combination therapy

Outcome Measures

Primary Outcomes (2)

• DLT

  The incidence of DLTs in PM1021 monotherapy and PM1021 combination therapy with PM8001, respectively.

  Part A: up to 21 days. Part B: up to 21 days.

• AEs and SAEs

  The incidence and severity of treatment-emergent adverse events (TEAEs) and treatment related adverse events (TRAEs) graded according to NCI-CTCAE v5.0.

  Up to 30 days after last treatment

Secondary Outcomes (14)

• RP2D

  Up to 30 days after last treatment

• Maximum observed concentration (Cmax)

  Up to 30 days after last treatment

• Time to Cmax (Tmax)

  Up to 30 days after last treatment

• Trough concentrations

  Up to 30 days after last treatment

• Area under the concentration-time curve (AUC0-t)

  Up to 30 days after last treatment

Study Arms (1)

PM1021 150 mg, 450 mg, 900 mg or 1200 mg monotherapy or in combination with PM8001 (20 mg/kg)

EXPERIMENTAL

Participants will be administered with PM1021 on Part A Day 1. Participants will be administered with PM1021 and PM8001 on Part B Day 1. PM1021 and PM8001 combination therapy administrated every 3 weeks from Part C Day 1 until disease progression, intolerable toxicity, until the patient withdraws/is withdrawn, or study completion.

Drug: PM1021, PM8001

Interventions

PM1021, PM8001 DRUG

Participants will be administered with PM1021 on Part A Day 1. Participants will be administered with PM1021 and PM8001 on Part B Day 1. PM1021 and PM8001 combination therapy administrated every 3 weeks from Part C Day 1 until disease progression, intolerable toxicity, until the patient withdraws/is withdrawn, or study completion.

PM1021 150 mg, 450 mg, 900 mg or 1200 mg monotherapy or in combination with PM8001 (20 mg/kg)

Eligibility Criteria

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

You may qualify if:

• Male or female, aged 18-75 years (inclusive) on the day of signing the consent form;
• Patients with histologically or cytologically confirmed advanced solid tumours;
• Evidence of adequate organ function;
• Eastern Cooperative Oncology Group score is 0-1;
• Expected survival greater than or equal to 12 weeks in the opinion of the Investigator;
• Female patients must:
• Be of non-child-bearing potential i.e. surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before the Screening visit) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone level consistent with postmenopausal status, per local laboratory guidelines), or
• If of child-bearing potential, must agree not to attempt to become pregnant, must not donate ova, and, if engaging in sexual intercourse with a male partner, must agree to use an acceptable method(s) of contraception from signing the consent form until at least 5 months after the last dose of study drug;
• Male patients must agree not to donate sperm and if engaging in sexual intercourse with a female partner who could become pregnant, must agree to use an acceptable method of contraception from signing the consent form until at least 5 months after the last dose of study drug;

You may not qualify if:

• History of serious allergic diseases, history of serious drug allergy or known allergy to any component of the drugs in this study;
• Clinically significant active infection within 2 weeks prior to the start of study treatment;
• Previously received treatment with PD-L1 or TIGIT monoclonal/bispecific antibody, or targeting TGF-β drugs;
• Previously received immunotherapy and have experienced ≥ Grade 3 immunotherapy-related adverse events or ≥ Grade 2 immune-related myocarditis;
• The adverse reactions of previous anti-tumour treatment have not recovered to NCI-CTCAE V5.0 Grade ≤ 1;
• Patients who have received the following therapies or drugs prior to the start of study treatment:
• Patients who have undergone major organ surgery within 28 days prior to the start of study treatment;
• Patients who have been vaccinated with live or live-attenuated vaccine within 28 days prior to the start of study treatment;
• Patients who have received chemotherapy, radical/extensive radiotherapy, endocrine therapy and other anti-tumour drug therapies within 4 weeks prior to the start of study treatment;
• Patients who have received systemic glucocorticoids (prednisone \>10 mg/day or equivalent dose of similar drugs) or other immunosuppressive therapies within 14 days prior to the start of study treatment;
• Patients with known meningeal metastases or uncontrollable central nervous system metastases, manifested as cerebral edema, spinal cord compression and/or progressive growth;
• Patients with active or previous autoimmune diseases with possible recurrence, except for clinically stable patients with autoimmune thyroid disease and type I diabetes;
• Patients who have had other active malignant tumours within 5 years prior to the start of study treatment, except for those which can be treated locally and have been cured;
• Patients with a history of serious cardio-cerebrovascular diseases;
• Presence of poorly controlled diabetes prior to the start of study treatment;

Sponsors & Collaborators

• Biotheus Inc.: lead

Study Officials

• Vineet Kwatra

  Cancer Research South Australia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vineet Kwatra, PhD

CONTACT

+61 883 592 565; vineet.kwatra@aoah.com.au

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: September 8, 2022
• First Posted: September 13, 2022
• Study Start: October 30, 2023
• Primary Completion: October 30, 2024
• Study Completion: December 31, 2025
• Last Updated: February 8, 2023

Record last verified: 2022-09

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.