Advanced Solid TumoursPhase 1NCT05537051
A Study of PM1021 (Anti-TIGIT) With or Without PM8001 (Anti-PD-L1/TGF-β) in Patients With Advanced Solid Tumours
A Phase 1 study testing PM1021, PM8001 in people with Advanced Solid Tumours, run by Biotheus Inc..
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced Solid Tumours
- What is being tested?
- PM1021, PM8001
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 30 Oct 2023to 31 Dec 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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;
Who cannot join
- 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:
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- 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;
- Current presence of uncontrollable pleural, pericardial and peritoneal effusions;
- History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
- Patients unlikely to comply with the clinical study protocol;
- Known substance abuse or medical, psychological, or social conditions that, in the opinion of the Investigator, may interfere with the patient's participation in the clinical study or evaluation of the clinical study results;
- History of immunodeficiency, including a positive HIV antibody test;
- Active hepatitis B, hepatitis C, or syphilis infection;
- Patients with a positive coronavirus (COVID-19) nucleic acid test at screening;
- Women who are pregnant or breastfeeding;
- Other conditions deemed by the Investigator to be inappropriate for participation in this study.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of PM1021 (Anti-TIGIT) Monotherapy and PM1021 in Combination With PM8001 (Anti-PD-L1/TGF-β) in Patients With Advanced Solid Tumours
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.
Read the detailed description
This is a single-arm, open-label, Phase I study including a first-in-human study for PM1021, and the combination therapy of PM1021 with PM8001. The study will be following the accelerated titration design and the classic 3+3 design, and dose escalation will be investigated for PM1021 monotherapy (Part A) and in combination with PM8001 (Part B), respectively. In the absence of DLTs in Parts A and B, patients will continue to receive combination therapy (Part C) until disease progression, intolerable toxicity, until the patient withdraws/is withdrawn, or study completion.
Up to 30 patients are planned to be enrolled. Four dose levels (150mg, 450 mg, 900 mg, and 1200 mg) of PM1021 with or without PM8001 (20 mg/kg) treatment will be explored in this study.
- Conditions
- Advanced Solid Tumours
- Being tested
- PM1021, PM8001
- Keywords
- PM1021, PM8001, monotherapy, combination therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PM1021, PM8001Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: PM1021, PM8001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
DLT
The incidence of DLTs in PM1021 monotherapy and PM1021 combination therapy with PM8001, respectively.
Measured: 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.
Measured: Up to 30 days after last treatment
Secondary outcomes (14)
RP2D
To determine the recommended Phase II Dose (RP2D) of PM1021 monotherapy, and PM1021 combination therapy with PM8001, respectively.
Measured: Up to 30 days after last treatment
Maximum observed concentration (Cmax)
To evaluate the Cmax of PM1021 monotherapy, and PM1021 combination therapy with PM8001, respectively
Measured: Up to 30 days after last treatment
Time to Cmax (Tmax)
To evaluate the Tmax of PM1021 monotherapy, and PM1021 combination therapy with PM8001, respectively
Measured: Up to 30 days after last treatment
Trough concentrations
To evaluate the trough concentrations of PM1021 monotherapy, and PM1021 combination therapy with PM8001, respectively
Measured: Up to 30 days after last treatment
Area under the concentration-time curve (AUC0-t)
To evaluate the AUC0-t of PM1021 monotherapy, and PM1021 combination therapy with PM8001, respectively
Measured: Up to 30 days after last treatment
Apparent terminal elimination half-life (t1/2)
To evaluate the t1/2 of PM1021 monotherapy, and PM1021 combination therapy with PM8001, respectively
Measured: Up to 30 days after last treatment
Accumulation ratio calculated based on Cmax (Rac_Cmax)
To evaluate the Rac_Cmax of PM1021 monotherapy, and PM1021 combination therapy with PM8001, respectively
Measured: Up to 30 days after last treatment
Objective response rate (ORR)
Defined as the number of patients with best overall response of confirmed CR or PR per RECIST 1.1 divided by the patients with at least one tumour imaging evaluation.
Measured: Up to 30 days after last treatment
Disease control rate (DCR)
Defined as the percentage of patients who have achieved CR, PR, Non-CR/Non- PD, or SD in the study.
Measured: Up to 30 days after last treatment
Progression-free survival (PFS)
Defined as the time from the date of first dose of study drug to the first observation of documented disease progression per RECIST 1.1 as determined by the Investigators or death due to any cause, whichever occurs first.
Measured: Up to 30 days after last treatment
Overall survival (OS)
Defined as the time from the date of first dose of study drug to the date of documented death due to any cause.
Measured: Up to 30 days after last treatment
Time to Response (TTR)
Defined as the duration from the date of first dose of study drug until date of first documented CR or PR.
Measured: Up to 30 days after last treatment
Duration of Response (DOR)
Defined as the time from the earliest date of documented CR or PR until documented disease progression or death (by any cause, in the absence of progression) as determined by the Investigators using RECIST 1.1.
Measured: Up to 30 days after last treatment
Anti-drug antibody (ADA)
To evaluate the incidence of ADA to PM1021 and PM8001.
Measured: Up to 30 days after last treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Sep 2022
- Study start30 Oct 2023 (estimated)
- Primary completion30 Oct 2024 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumoursStudies of the same condition, open and under way.
- More trials run by Biotheus Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Biotheus Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Vineet Kwatra, Principal investigator, Cancer Research South Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05537051
- Sponsor's protocol ID
- PM10218001-A001C-ST-R
- Status last verified
- Sep 2022
- First submitted
- 8 Sep 2022
- Last updated
- 8 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data will be published or presented for publications (poster, abstract, articles or papers) or maked any presentations.
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of PM1021 (Anti-TIGIT) Monotherapy and PM1021 in Combination With PM8001 (Anti-PD-L1/TGF-β) in Patients With Advanced Solid Tumours
- ClinicalTrials.gov ID
- NCT05537051
- Acronym / sponsor ID
- PM10218001-A001C-ST-R
- Conditions
- Advanced Solid Tumours
- Keywords
- PM1021, PM8001, monotherapy, combination therapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Biotheus Inc.Industry (pharma, biotech, devices)
- Study start
- 30 Oct 2023 (estimated)
- Primary completion
- 30 Oct 2024 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 13 Sep 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a single-arm, open-label, Phase I study including a first-in-human study for PM1021, and the combination therapy of PM1021 with PM8001. The study will be following the accelerated titration design and the classic 3+3 design, and dose escalation will be investigated for PM1021 monotherapy (Part A) and in combination with PM8001 (Part B), respectively. In the absence of DLTs in Parts A and B, patients will continue to receive combination therapy (Part C) until disease progression, intolerable toxicity, until the patient withdraws/is withdrawn, or study completion.
Up to 30 patients are planned to be enrolled. Four dose levels (150mg, 450 mg, 900 mg, and 1200 mg) of PM1021 with or without PM8001 (20 mg/kg) treatment will be explored in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PM1021 150 mg, 450 mg, 900 mg or 1200 mg monotherapy or in combination with PM8001 (20 mg/kg) | Experimental | Drug: PM1021, PM8001Participants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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;
Key exclusion criteria (24 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PM1021, PM8001Participants 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 150 mg, 450 mg, 900 mg or 1200 mg monotherapy or in combination with PM8001 (20 mg/kg) |
Primary outcome
DLT
Time frame: Part A: up to 21 days. Part B: up to 21 days.
The incidence of DLTs in PM1021 monotherapy and PM1021 combination therapy with PM8001, respectively.
AEs and SAEs
Time frame: Up to 30 days after last treatment
The incidence and severity of treatment-emergent adverse events (TEAEs) and treatment related adverse events (TRAEs) graded according to NCI-CTCAE v5.0.
14 secondary outcomes
RP2D
Time frame: Up to 30 days after last treatment
Maximum observed concentration (Cmax)
Time frame: Up to 30 days after last treatment
Time to Cmax (Tmax)
Time frame: Up to 30 days after last treatment
Trough concentrations
Time frame: Up to 30 days after last treatment
Area under the concentration-time curve (AUC0-t)
Time frame: Up to 30 days after last treatment
Apparent terminal elimination half-life (t1/2)
Time frame: Up to 30 days after last treatment
Accumulation ratio calculated based on Cmax (Rac_Cmax)
Time frame: Up to 30 days after last treatment
Objective response rate (ORR)
Time frame: Up to 30 days after last treatment
Disease control rate (DCR)
Time frame: Up to 30 days after last treatment
Progression-free survival (PFS)
Time frame: Up to 30 days after last treatment
Overall survival (OS)
Time frame: Up to 30 days after last treatment
Time to Response (TTR)
Time frame: Up to 30 days after last treatment
Duration of Response (DOR)
Time frame: Up to 30 days after last treatment
Anti-drug antibody (ADA)
Time frame: Up to 30 days after last treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
- Individual participant dataSharing planned: Yes. The data will be published or presented for publications (poster, abstract, articles or papers) or maked any presentations.
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A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK043 in Patients With Advanced Solid Tumor
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A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vineet Kwatra principal investigator
Cancer Research South Australia
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PM1021, PM8001 in people with Advanced Solid Tumours, run by Biotheus Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Vineet Kwatra, PhD (+61 883 592 565, vineet.kwatra@aoah.com.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DLT (time frame: Part A: up to 21 days. Part B: up to 21 days.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.