Neoplasms

Digestive System Diseases

All Conditions

Skin and Connective Tissue Diseases

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Rare Diseases

Esophageal Neoplasms

Carcinoma

Cholangiocarcinoma

Adenocarcinoma

Melanoma

Carcinoma, Squamous Cell

Sarcoma

Ichthyosis, X-Linked

Squamous Cell Carcinoma of Head and Neck

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neoplasms, Glandular and Epithelial

Neoplasms, Connective and Soft Tissue

Head and Neck Neoplasms

Esophageal Diseases

Esophageal Cancer

Bile Duct Cancer

Soft Tissue Sarcoma

Neuroendocrine Tumor

Neuroepithelioma

Up to 30 patients with FAP-avid solid tumors.

\[Ga-68\]-PNT6555 IV administered as imaging agent for PET/CT

[Ga-68]-PNT6555

Patients with FAP-avid disease as determined by the \[Ga-68\]-PNT6555 screening PET/CT will receive \[Lu-177\]-PNT6555 at a fixed dose level for up to 6 doses at an interval of 6 weeks between each dose.

[Lu-177]-PNT6555

Jessica Jensen

This Phase 1 study will evaluate the safety and tolerability of \[Ga-68\]-PNT6555 and \[Lu-177\]-PNT6555 in subjects with select solid tumors that have FAP over-expression, in order to determine a recommended Phase 2 dose.

FAPi Radioligand OpeN-Label, Phase 1 Study to Evaluate Safety, Tolerability and DosImetry of [Lu-177]-PNT6555; A Dose Escalation Study for TReatment of Patients With Select Solid Tumors (FRONTIER)

Objective response rate (ORR) based on RECIST 1.1

Absorbed dose estimates (Gy) in tumor lesions for \[Lu-177\]-PNT6555

\[Ga-68\]-PNT6555 SUV at 0 - 60, 60, 90, and 120 min of tumor lesions and normal organs

Occurrence of Treatment emergent adverse events as per CTCAE v5.0

Occurrence of adverse events for \[Ga-68\]-PNT6555 as per CTCAE v5.0

Absorbed dose estimates (Gy) in normal organs for \[Lu-177\]-PNT6555

Absorbed dose estimates (Gy) in normal organs for \[Ga-68\]-PNT6555

Anatomic distribution of \[Ga-68\]-PNT6555

Maximum and average standardized uptake values of \[Ga-68\]-PNT6555 in tumor lesions

POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company

Respiratory Tract (Lung and Bronchial) Diseases

Pleural Effusion

Mesothelioma

Mesothelioma, Malignant

Adenoma

Neoplasms, Mesothelial

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Malignant Mesothelioma

Adoptive Transfer of re-directed FAP specific T cells in the pleural effusion

Adoptive Transfer of 10e6 re-directed T cells in the pleural effusion

Adoptive Transfer of re-directed T cells

Alessandra Curioni, MD

MPM patients are not eligible for surgical procedures like decortication or pleuro-pneumectomy and have a median survival of 12 months with palliative chemotherapy. Therefore, new therapeutic approaches are of crucial need in this clinical situation. This is a phase I trial for patients with malignant pleural mesothelioma with pleural effusion testing the safety of a fixed single dose of 1x10e6 adoptively transferred FAP-specific re-directed T cells given directly in the pleural effusion. Lymphocytes will be taken 21 days before transfer from peripheral blood. CD8 positive T cells will be isolated and re-programmed by retroviral transfer of a chimeric antigen receptor (CAR) recognizing FAP which serves as target structure in MPM.

* Trial with immunomodulatory product / biological

This is a phase I trial for patients with malignant pleural mesothelioma. A fixed single dose of adoptively transferred FAP-specific CD8 positive re-directed T cells will be given in the pleural effusion.

Three patients who are at the time point of screening not operable will be treated with re-directed T cells administered into the pleural effusion after completion of 3 cycles of palliative chemotherapy. In the case of one AE grade III/IV or one SAE - and the occurrence of DLT both judged to be treatment related by an independent safety monitoring board - the patient number will be expanded to 6 patients. The study will be stopped if one additional DLT occurs also judged to be treatment related.

Patients will be treated with 1x10e6 re-directed FAP-specific T cells injected in the pleural effusion. The study ends 35 days after adoptive T cell transfer. Re-directed FAP-specific T cells will be administered at day 0 (day 14 of the third cycle of palliative chemotherapy). The study is designed to demonstrate safety of 1x10e6 re-directed FAP-specific T cells. The next patient will be enrolled earliest, when the previous patient completed day +14 and the safety monitoring board has not declared any DLTs. The palliative chemotherapy is not part of the study protocol.

Adoptive Transfer of re-directed FAP-specific T cells

Re-directed T Cells for the Treatment (FAP)-Positive Malignant Pleural Mesothelioma

Phase I Study for the Adoptive Transfer of Re-directed FAP-specific T Cells in the Pleural Effusion of Patients With Malignant Pleural Mesothelioma.

Incidence and severity of treatment-related laboratory abnormalities, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version v4.03 criteria as grade III-IV. In the case of one AE grade III/IV or one SAE the safety monitoring board will judge whether the case is treatment related and whether it have to be counted as DLT.

University of Zurich

All Drugs and Chemicals

Immunomodulating Agents

The starting dose is 0.03 mg/kg every 3 weeks (q3w) and up to 6 dose levels are planned.

Study treatment will be administered as an intravenous (IV) infusion until progressive disease (PD), unacceptable toxicity, withdrawal of consent or other reasons to discontinue treatment occur, whichever comes first.

The starting dose is 0,5 mg/kg every week (q1w) and up to 3 dose levels are planned.

Study treatment will be administered as an intravenous (IV) infusion until progressive disease (PD), unacceptable toxicity, withdrawal of consent or other reasons to discontinue treatment occur, whichever comes first.

The study will start with dose-escalation cohorts to determine the recommended dose for expansion (RDE) or the maximum tolerated dose (MTD).

Once the RDE (or MTD) has been determined, a safety expansion cohort will be opened and additional patients will be treated with MP0317 monotherapy at this dose to confirm safety in a larger population.

Study treatment will be administered every 3 weeks (q3w) as an intravenous (IV) infusion until progressive disease (PD), unacceptable toxicity, withdrawal of consent or other reasons to discontinue treatment occur, whichever comes first. Treatment beyond PD will be allowed as per Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST).

MP0317, a tri-specific fibroblast activation protein (FAP) x CD40 DARPin® drug candidate (q3w regimen)

The study will start with dose-escalation cohorts to determine the recommended dose for expansion (RDE) or the maximum tolerated dose (MTD).

Once the RDE (or MTD) has been determined, a safety expansion cohort will be opened and additional patients will be treated with MP0317 monotherapy at this dose to confirm safety in a larger population.

Study treatment will be administered every week (q1w) as an intravenous (IV) infusion until progressive disease (PD), unacceptable toxicity, withdrawal of consent or other reasons to discontinue treatment occur, whichever comes first. Treatment beyond PD will be allowed as per Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST).

MP0317, a tri-specific fibroblast activation protein (FAP) x CD40 DARPin® drug candidate (q1w regimen)

This study is investigating a new experimental therapy, MP0317, a DARPin® drug candidate targeting fibroblast activation protein (FAP) and CD40. Preclinical studies suggest that MP0317 may provide benefit for the treatment of tumors known to express high levels of FAP and for which approved therapies have been exhausted. This is the first study of MP0317 in humans and its main purpose is to test its safety and tolerability in patients with advanced solid tumors. This study will also examine the blood levels of MP0317 at several increasing dose levels and a recommended dose for further development will be determined. The recommended dose will be tested in a second part of the study to confirm safety and to further assess the preliminary biologic and anti-tumor activity.

First-in-human Safety and Tolerability of MP0317 in Patients With Relapsed/Refractory Advanced Solid Tumors

A Phase 1, First-in-human, Multicenter, Open-label, Dose-escalation Study to Characterize the Safety and Tolerability of MP0317 in Patients With Relapsed/Refractory Advanced Solid Tumors

According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

DLTs will be reviewed as a subset of AEs that occur within 4 weeks after first study drug administration

Based on occurrence of DLTs within an adaptive study design following Bayesian Logistic Regression Model (BLRM)

Based on incidence and nature of DLTs, and incidence, nature, and severity of AEs and SAEs

Including parameters like maximum serum concentration (Cmax), time at Cmax (Tmax), minimal serum concentration (Cmin)

Proportion of participants with complete response (CR) and partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST)

Best overall response (BOR) of CR, PR or stable disease (SD) lasting 4 or more weeks following first study drug administration

For participants with CR or PR, DOR will be calculated as the time from CR or PR to progressive disease (PD) or death.

Time from first study drug administration to PD

Time from first study drug administration to PD or death

Time from first study drug administration to death of any cause

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
FAPi Radioligand OpeN-Label, Phase 1 Study to Evaluate Safety, Tolerability and DosImetry of [Lu-177]-PNT6555; A Dose Escalation Study for TReatment of Patients With Select Solid Tumors (FRONTIER)	NCT05432193	Pancreatic Duct... Colorectal Canc... Esophageal Canc... Melanoma (Skin) Soft Tissue Sar... Head and Neck S... Cholangiocarcin...	[Ga-68]-PNT6555 [Lu-177]-PNT655...	18 Years -	POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company
Re-directed T Cells for the Treatment (FAP)-Positive Malignant Pleural Mesothelioma	NCT01722149	Malignant Pleur...	Adoptive Transf...	18 Years - 75 Years	University of Zurich
First-in-human Safety and Tolerability of MP0317 in Patients With Relapsed/Refractory Advanced Solid Tumors	NCT05098405	Advanced Malign...	MP0317, a tri-s... MP0317, a tri-s...	18 Years -	Molecular Partners AG
Re-directed T Cells for the Treatment (FAP)-Positive Malignant Pleural Mesothelioma	NCT01722149	Malignant Pleur...	Adoptive Transf...	18 Years - 75 Years	University of Zurich
FAPi Radioligand OpeN-Label, Phase 1 Study to Evaluate Safety, Tolerability and DosImetry of [Lu-177]-PNT6555; A Dose Escalation Study for TReatment of Patients With Select Solid Tumors (FRONTIER)	NCT05432193	Pancreatic Duct... Colorectal Canc... Esophageal Canc... Melanoma (Skin) Soft Tissue Sar... Head and Neck S... Cholangiocarcin...	[Ga-68]-PNT6555 [Lu-177]-PNT655...	18 Years -	POINT Biopharma, a wholly owned subsidiary of Eli Lilly and Company
First-in-human Safety and Tolerability of MP0317 in Patients With Relapsed/Refractory Advanced Solid Tumors	NCT05098405	Advanced Malign...	MP0317, a tri-s... MP0317, a tri-s...	18 Years -	Molecular Partners AG

Spots Global Cancer Trial Database for fibroblast activation protein