Participants receive PM1009 intravenously, every 2 weeks

PM1009 injection

Xuelian Xing

Ye Guo

The study is being conducted to evaluate safety, tolerability, pharmacokinetics and preliminary efficacy of PM1009 for patients with advanced tumors, also to explore the recommended Phase Ⅱ Dose（RP2D） of PM1009.

PM1009 is a new novel fully human anti-TIGIT x PVRIG bispecific antibody, containing a wildtype IgG1 Fc and has high monovalent affinity to each target, it can binds to both TIGIT and PVRIG overexpressing target cells and binds to TIGIT and PVRIG simultaneously.

This is a single-arm, open-label, Phase I study contains dose escalation stage and dose expansion stage.

The dose escalation stage will be following the accelerated titration design and the classic 3+3 design, with a planned enrollment of 10 to 24 patients with advanced tumors.

The dose expansion stage will be used safe and tolerable doses, with a planned enrollment of 30 patients with advanced tumors.

Patients sequentially receive PM1009 120 mg, 300 mg, 600 mg, 1200 mg, intravenously, Q2W

A Study of PM1009 (Anti-TIGIT/PVRIG) in Patients With Advanced Tumours

A Phase I Study to Evaluate the Tolerability, Safety, Pharmacokinetic Characteristics and Preliminary Efficacy of PM1009 (Anti-TIGIT/PVRIG) in Patients With Advanced Tumors

The data will be published or presented for publications (poster, abstract, articles or papers) or maked any presentations.

T-lymphocyte phenotypes in peripheral blood

Occurrence of DLT after receiving PM1009 injection

To determine the RP2D of PM1009 injection

To evaluate the Cmax of PM1009 monotherapy

To evaluate the Tmax of PM1009 monotherapy

To evaluate the Cmin of PM1009 monotherapy

To evaluate the Ctrough of PM1009 monotherapy

To evaluate the AUC0-last of PM1009 monotherapy

To evaluate the AUC0-tau of PM1009 monotherapy

To evaluate the t1/2 of PM1009 monotherapy

To evaluate the Rac_Cmax of PM1009 monotherapy

To evaluate the Rac_AUC of PM1009 monotherapy

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

Defined as the percentage of patients who have achieved CR, PR, Non-CR/Non-PD, or SD in the study.

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.

Defined as the time from the date of first dose of study drug to the date of documented death due to any cause.

To evaluate the incidence of ADA to PM1009 injection

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

Biotheus Inc.

Neoplasms

Symptoms and General Pathology

All Conditions

Neoplasm Metastasis

Neoplastic Processes

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Ipilimumab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

* PEXA-VEC (Pexastimogene devacirepvec): Oncolytic live replicating virus, Recombinant vaccinia virus GM-GCF of Classe 1, administered by Intra-tumoral injection with fixed-dosage regimen of 1x109 pfu (9.0 Log pfu)/ injection. Up to 5 IT injections, at Week 1 Day 1, Week 3 Day 1, Week 5 Day 1 and Week 9 Day 1, and one additional IT treatment allowed in case of disease progression following a documented objective response at W12. Provided by Transgene.
* IPILIMUMAB: Anti-CTLA-4 monoclonal antibody (IgG1k) produced in CHO cells by recombinant DNA technology, administered by Intra-tumoral injection. Up to 4 IT injections at Week 3 Day 1, Week 5 Day 1 and Week 9 Day 1, and one additional IT treatment allowed In case of disease progression following a documented objective response at W12. Four dose levels of ipilimumab will be tested in dose escalation step: 2.5mg, 5mg, 7.5mg, 10mg, 20mg or 40 mg.

IT Injections will be performed by a radiologist using imaging-guidance, ultrasound or computed tomography (CT). The dose to be injected could be divided between 1 to 5 tumor lesions.

Pexa-Vec

Aurélien MARABELLE, MD, PhD

The success of anti-CTLA4 therapy has inaugurated a paradigm shift in oncology where drugs target the immune system rather than cancer cells in order to stimulate the anti-tumor immune response. In situ immunization is a strategy where immunomodulatory products such as pathogens are injected into one tumor site in order to trigger a systemic anti-tumor immune response. Of importance, pre-clinical rationale has demonstrated that combination of anti-CTLA4 therapy together with intra-tumoral (IT) oncolytic virus can overcome primary resistance to systemic anti-CTLA4 therapy. Pexastimogene Devacirepvec (Pexa-Vec) is one of the new vaccinia oncolytic viruses genetically modified to express GM-CSF. This new and innovative oncolytic virotherapy should therefore synergize with anti-CTLA4 therapy via virus-induced tumor cell death \& tumor-antigen release, GM-CSF-induced recruitment/maturation/activation of antigen presenting cells, and anti-CTLA4-induced Treg blockade/depletion. Intra-tumoral delivery of immunostimulating agents should, therefore, provide lower toxicity of mAb targeting immune checkpoints. Of note, IT injections of GM-CSF-encoding oncolytic viruses have already been shown to induce immune-mediated tumor responses on local (injected) and distant (not injected) tumor sites. In solid injectable refractory/relapsing metastatic tumors, we make the hypothesis that the addition of Pexa-Vec to IT ipilimumab (anti-CTLA4 Ab) will overcome primary/secondary resistance to standard therapy and/or immunotherapy with a better in situ tumor antigen specific T-cell priming. Our proposal is to conduct a 2-part Phase I clinical trial in order to define the feasibility, the safety and the anti-tumor effects of intra-tumoral injections of ipilimumab in combination with the oncolytic virus Pexa-Vec. Dose escalation step will define the MTD and RP2D of that in situ immunization strategy. Expansion part will assess the anti-tumor effect of the combination.

The study is a proof of concept, open label, multicentric, 2-parts, Phase I dose escalation trial. In dose selection part (any histological types except HCC), patients will be treated with an IT boost injection with Pexa-Vec (fixed dose of 1x109 pfu / injection ) alone at Week 1 followed by IT injections of Pexa-Vec + ipilimumab (up to 4 dose levels) at Weeks 3, 5 and 9. The dose escalation part will follow a classical 3+3 design. 3 to 6 patients will be enrolled at each DL (Dose Level) depending of the number of Dose Limiting Toxicity (DLT) observed. At the end of each DL cohort, a teleconference (Dose escalation meeting) will be organized with the sponsor, in order to select the dose for the next cohort. In Expansion cohorts ( up to 3 cohorts) patients will be treated with an IT boost injection with Pexa-Vec alone (fixed dose of 1x109 pfu / injection) at Week 1 followed by IT injections of Pexa-Vec + ipilimumab (RP2D) at Weeks 3, 5 and 9. In both parts, the treatment with both IMPs should be continued as per protocol until Withdrawal of consent, Disease progression as per irRC (immune related response criteria), General or specific changes in the patient's condition that render the patient unacceptable for further treatment in the judgment of the investigator, Pregnancy or Unacceptable adverse events(s) including DLTs.

Immunization Strategy With Intra-tumoral Injections of Pexa-Vec With Ipilimumab in Metastatic / Advanced Solid Tumors.

A Phase I Dose Escalation Trial Evaluating the Impact of an in Situ Immunization Strategy With Intra-Tumoral Injections of Pexa-Vec in Combination With Ipilimumab in Metastatic / Advanced Solid Tumors With Injectable Lesions.

DLT is defined as the occurrence of any of the following events evaluated as related to study drugs and occurring during the first 5 weeks (Part A) of investigative treatment(s): any Grade ≥ 4 treatment related toxicity, any Grade≥ 3 treatment related toxicity lasting more than 7 days (except for flu-like symptoms that respond to standard therapies.), any Grade ≥ 3 treatment related acute immune related AE involving major end organs, Grade ≥ 3 injection site reaction, Any other study drug related toxicity considered significant enough to be qualified as DLT in the opinion of the investigators after discussion with the sponsor. Indeed, as a principle in this Phase I study, any toxicity that the investigator or the sponsor determines to be dose-limiting, regardless of the grade, may be considered as a DLT.

The 3-month objective response rate is defined by the percentage of patients having complete response (CR) or partial response (PR) according to immune related Response Criteria (irRC).

defined by the percentage of patients having complete response (CR) or partial response (PR) according to irRC (immune related Response Criteria) and to RECIST 1.1 criteria.

defined by the percentage of patients having complete response (CR) or partial response (PR) as best response at any time point according to irRC and to RECIST 1.1 criteria.

defined by the rate of patients having complete response (CR), partial response (PR) or stable disease (SD) according to irRC and to RECIST 1.1 criteria.

OR defined as at least 50% decrease of tumor size

PFS will be estimated using Kaplan Meier method.

All AEs will be graded according to NCI-CTCAE, Version 4

Transgene

Centre Leon Berard

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Sarcoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Connective and Soft Tissue

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

Soft Tissue Sarcoma

Durvalumab

Trabectedin

Antineoplastic Agents, Alkylating

Alkylating Agents

Trabectedin will be administered intraveinously, on day 1 of each cycle, every three weeks, as appropriate for assigned dose level.

Durvalumab will be administered intraveinously, at fixed doses of 1120 mg (equivalent to 15 mg/kg), on day 2 of each cycle, every three weeks.

Dose Escalation : 3 doses of trabectedin given in combination with durvalumab (fixed dose) will be investigated.

A treatment cycle consists of 3 weeks. Treatment may continue until disease progression or study discontinuation (withdrawal of consent, intercurrent illness, unacceptable adverse event or any other changes unacceptable for further treatment, etc.).

Expansion cohorts: Once the Maximum Tolerated Dose (MTD) has been defined, the expansion cohorts will be opened. All patients will be treated at the MTD of Trabectedin (as defined in the dose escalation part of the trial) given in association with Durvalumab with the same schedule as in the dose escalation part of the trial.

Combination of trabectedin with durvalumab

A phase Ib trial study of trabectedin when prescribed in combination with durvalumab in locally advanced/unresectable soft-tissue sarcoma and ovarian carcinomas.

This is a multicenter, prospective phase Ib trial based on a dose escalation study design (3+3 traditional design) assessing three dose levels of Trabectedin given with durvalumab, followed by two expansion cohorts once the MTD is established.

This is a multicenter, prospective open-labeled phase Ib trial based on a dose escalation study design (3+3 traditional design) assessing three dose levels of trabectedin when prescribed in combination with durvalumab followed by two expansion cohorts (Soft-tissue sarcomas and ovarian carcinomas) once the MTD is established

Trabectedin Combined With Durvalumab in Patients With Advanced Pretreated Soft-tissue Sarcomas and Ovarian Carcinomas.

Trabectedin Combined With Durvalumab (MEDI4736) in Patients With Advanced Pretreated Soft-tissue Sarcomas and Ovarian Carcinomas. A Phase Ib Study.

Identification of predictive signature in responders by sequencing tumor sample

AstraZeneca

PharmaMar

Institut Bergonié

Dose escalation of indibulin given twice daily for up to 6 months

indibulin

Jonathan Lewis, MD

Dose escalating study of orally administered indibulin at twice daily schedule in subjects with solid tumors.

Phase I Study in Advanced Solid Tumors

IBL1002:Phase I Study of Indibulin in Advanced Solid Tumors

Alaunos Therapeutics

Digestive System Diseases

Skin and Connective Tissue Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Uterine Cervical Neoplasms

Esophageal Neoplasms

Breast Neoplasms

Triple Negative Breast Neoplasms

Carcinoma, Non-Small-Cell Lung

Stomach Neoplasms

Lung Neoplasms

Breast Diseases

Skin Diseases

Esophageal Cancer

Stomach Cancer

According to the cell transfusion protocol, GK01 cells were given at a certain dose level to observe the safety and tolerability of the patients after the transfusion, explore the pharmacokinetic/pharmacodynamic characteristics after the transfusion, and preliminarily evaluate the effectiveness of the experimental drug GK01 cells according to the RECIST 1.1 standard.

The strengthened T cells are re-infused into the patient to achieve the killing effect

TCR T-cells

Yi Zhang, Doctor

Ge Zhang

This trial plans to enroll many patients with advanced solid tumors to complete GK01 cell transfusion, including but not limited to advanced gastric cancer, esophageal cancer, cervical cancer, triple-negative breast cancer, and non-small cell lung cancer. For patients with advanced solid tumors eligible for inclusion, autologous tumor-reactive T cells (experimental drug GK01) were cultured and prepared, and a certain dose of GK01 cells was given according to the cell transfusion plan, and the safety and tolerability of the patients after transfusion were observed. Exploratory evaluation of pharmacokinetic/pharmacodynamic profiles following reinfusion and initial evaluation of efficacy of investigational drug GK01 cells according to RECIST 1.1 criteria.

a Single-arm, Single-center, Open Clinical Study

Clinical Study on the Safety and Efficacy of GK01 Autologous Tumor-reactive T Cells (TRT) in Patients With Advanced Solid Tumors

To evaluate the safety and tolerability of GK01 autologous tumor-reactive T cells (TRT) in patients with advanced solid tumors.

To explore the specificity and persistence of GK01 autologous tumor-reactive T cells (TRT) expansion in patients with advanced solid tumors

To evaluate the initial efficacy of GK01 autologous tumor-reactive T cells (TRT) in the treatment of patients with advanced solid tumors based on RECIST 1.1 criteria

Beijing Geekgene Technology Co., LTD

In the phase, five dose groups were proposed.The frequency of administration was once a week, and the treatment cycle was 3 weeks.

QLF32004

Jin Li

To determine the safety, tolerability, and recommended dose (RP2D) of QLF32004 in patients with advanced malignancies.

QLF32004 Injection for the Treatment of Patients With Advanced Malignant Tumors

Phase Ia Clinical Study of Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of QLF32004 for Injection Monotherapy in Patients With Advanced Malignant Tumors

Qilu Pharmaceutical Co., Ltd.

Amino Acids

Gefitinib

Cediranib

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine Kinase Inhibitors

Tyrosine

AZD2171

ZD1839

Nick Botwood, BSc, MBBS, MRCP, MFPM

G Giaccone, Prof

Phase I AZD2171 in combination with ZD1839 study recruiting patients with advanced cancer

Phase I Study of AZD2171 co-Administered With Fixed Multiple Oral Doses of ZD1839 in Patients With Advanced Cancer

A Phase I Open-Label Study to Assess the Safety, Tolerability and PK of Ascending Multiple Oral Doses of AZD2171 When co-Administered With Fixed Multiple Oral Doses of ZD1839 (250mg or 500mg Once Daily) in Patients With Advanced Cancer

Subjects will receive PM1032 by intravenous administration.

PM1032 injection

Xiying Dong

Lihua Wu

Yong Li

The study is being conducted to evaluate safety, tolerability, pharmacokinetics and preliminary efficacy of PM1032 for patients with advanced tumors, also to explore the recommended Phase Ⅱ Dose（RP2D） of PM1032.

PM1032 is a Bispecific Antibody Targeting CLDN18.2 and 4-1BB.

In dose escalation stage, three subjects will be enrolled at the protocol starting dose of PM1032 for 21 Days DLT observation, followed by same dose every 2 weeks (Q2W) until they meet the discontinuation criteria.

Dose escalation will proceed to the next dose level according to the 3+3 design.

Dose expansion stage of the study will be initiated at the Sponsor's discretion at the dose level and treatment schedule which was established as the recommended Phase 2 dose (RP2D) in the dose escalation stage.

Phase I/IIa Study for PM1032 in the Treatment of Patients With Advanced Solid Tumors

A Phase I/IIa Study to Evaluate the Tolerance, Safety, Pharmacokinetic Characteristics and Preliminary Efficacy of PM1032 in Patients With Advanced Solid Tumors

Occurrence of DLT after receiving PM1032 injection

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of PM1009 (Anti-TIGIT/PVRIG) in Patients With Advanced Tumours	NCT05607563	Advanced Tumor	PM1009 injectio...	18 Years - 75 Years	Biotheus Inc.
Immunization Strategy With Intra-tumoral Injections of Pexa-Vec With Ipilimumab in Metastatic / Advanced Solid Tumors.	NCT02977156	Metastatic Tumo... Advanced Tumor	Pexa-Vec Ipilimumab	18 Years -	Centre Leon Berard
Trabectedin Combined With Durvalumab in Patients With Advanced Pretreated Soft-tissue Sarcomas and Ovarian Carcinomas.	NCT03085225	Ovarian Carcino... Soft Tissue Sar...	Combination of ...	18 Years -	Institut Bergonié
Phase I Study in Advanced Solid Tumors	NCT00591292	Solid Tumors	indibulin	18 Years -	Alaunos Therapeutics
a Single-arm, Single-center, Open Clinical Study	NCT06431100	Gastric Cancer Esophageal Canc... Cervical Cancer Non-Small Cell ... Triple Negative...	TCR T-cells	18 Years - 75 Years	Beijing Geekgene Technology Co., LTD
QLF32004 Injection for the Treatment of Patients With Advanced Malignant Tumors	NCT05108779	Advanced Tumor	QLF32004	18 Years - 75 Years	Qilu Pharmaceutical Co., Ltd.
Phase I Study of AZD2171 co-Administered With Fixed Multiple Oral Doses of ZD1839 in Patients With Advanced Cancer	NCT00502060	Advanced Tumor	AZD2171 ZD1839	18 Years -	AstraZeneca
Phase I/IIa Study for PM1032 in the Treatment of Patients With Advanced Solid Tumors	NCT05839106	Advanced Tumor	PM1032 injectio...	18 Years - 75 Years	Biotheus Inc.
Trabectedin Combined With Durvalumab in Patients With Advanced Pretreated Soft-tissue Sarcomas and Ovarian Carcinomas.	NCT03085225	Ovarian Carcino... Soft Tissue Sar...	Combination of ...	18 Years -	Institut Bergonié
A Study of PM1009 (Anti-TIGIT/PVRIG) in Patients With Advanced Tumours	NCT05607563	Advanced Tumor	PM1009 injectio...	18 Years - 75 Years	Biotheus Inc.
Phase I/IIa Study for PM1032 in the Treatment of Patients With Advanced Solid Tumors	NCT05839106	Advanced Tumor	PM1032 injectio...	18 Years - 75 Years	Biotheus Inc.

Spots Global Cancer Trial Database for advanced tumor