Symptoms and General Pathology

All Conditions

Death

Antineoplastic Agents

All Drugs and Chemicals

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Participants will receive SBRT combined with Cadonilimab. Cadonilimab will be administered, 6mg/kg, twice a week, intravenous until disease progression or intolerable toxicities or death. The first cycle of Cadonilimab was started within 3 days before and after the first fraction of SBRT treatment.

Cadonilimab

Participants will receive SBRT to one lesion or more lesions.

Stereotactic body radiotherapy

Hongqing Zhuang, M.D.

Yi Chen, M.D.

The goal of this multicenter prospective single-arm phase I/II study is to study the safety and efficacy stereotactic body radiotherapy (SBRT) combined with Cadonilimab for advanced refractory malignant solid tumors. The main questions it aims to answer are:

* How safe is this regimen of SBRT combined with Cadonilimab for advanced refractory malignant solid tumors?
* How effective is this regimen of SBRT combined with Cadonilimab for advanced refractory malignant solid tumors? Participants will receive SBRT combined with Cadonilimab until disease progression or intolerable toxicities or death.

The goal of this single center prospective single-arm phase I/II study is to study the safety and efficacy stereotactic body radiotherapy (SBRT) combined with Cadonilimab for advanced refractory malignant solid tumors. The primary endpoint is adverse event (AE) and the secondary endpoints are progression free survival, overall survival, overall response rate, and disease control rate.

Participants will receive SBRT combined with Cadonilimab. Cadonilimab will be administered, 6mg/kg, twice a week, intravenous until disease progression or intolerable toxicities or death. The first cycle of Cadonilimab was started within 3 days before and after the first fraction of SBRT treatment.

Participants will receive SBRT combined with Cadonilimab until disease progression or intolerable toxicities or death.

Stereotactic Body Radiotherapy Combined With Cadonilimab for Advanced Refractory Malignant Solid Tumors

Clinical Study of Stereotactic Body Radiotherapy Combined With Cadonilimab for the Treatment of Advanced Refractory Malignant Solid Tumors

The incidence of All adverse event (AE), treatment emergent AE (TEAE), treatment-related AE (TRAE), immune-related AE (irAE), serious AE (SAE) and radiation-related AE(rAE), the relevance and severity related with the study protocol.

The time from the date of treatment to the date of disease progression or death or last follow-up.

The time from the date of treatment to the date of death or last follow-up.

The rate of patients obtain complete response and partial response.

The rate of patients obtain complete response, partial response and stable disease.

Peking University Third Hospital

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Carcinoma

Lung Neoplasms

Lung Diseases

Recurrence

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunomodulating Agents

Patients whose tumors did not express programmed cell death-ligand 1 (PD-L1), i.e., tumor proportion score (TPS) \< 1% prior to ICI treatment and Patients with no available historical TPS for PD-L1 expression

Patients whose tumors expressed PD-L1 TPS ≥1% prior to ICI treatment

Patients, regardless of tumor PD-L1 TPS prior to ICI treatment, who are unable to safely undergo a surgical tumor resection for TIL generation

Patients, regardless of tumor PD-L1 expression status prior to ICI treatment, who have meet all inclusion/exclusion criteria except the requirement to have documented disease progression may elect to have the tumor harvest procedure and TIL production prior to disease progression on their current anticancer treatment. Documentation of progressive disease and identification of a target lesion for RECIST v1.1 assessment is required at Baseline for these patients.

Patients who were previously treated with LN-145 in Cohort 1, 2, 3, or 4.

A tumor sample is resected from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, patient is infused with autologous TIL (LN-145), followed by IL-2.

LN-145

A tumor sample is obtained by image-guided core biopsy from each patient and cultured ex vivo to expand the population of tumor infiltrating lymphocytes. After lymphodepleting chemotherapy including cyclophosphamide and fludarabine, patient is infused with autologous TIL (LN-145) followed by IL-2.

Iovance Biotherapeutics Study Team lungcelltherapy.com

Iovance Biotherapeutics Study Team

This is a prospective, open-label, multi-cohort, non-randomized, multicenter phase 2 study evaluating LN-145 in patients with metastatic non-small-cell lung cancer

LN-145 is a ready-to-infuse TIL therapy that utilizes an autologous TIL manufacturing process, as originally developed by the NCI and further optimized by Iovance for the treatment of patients with metastatic NSCLC. The cell transfer therapy used in this study involves patients receiving a non-myeloablative (NMA) lymphodepleting preparative regimen, followed by infusion of autologous TIL, then finally followed by the administration of IL-2.

Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer

A Phase 2 Multicenter Study of Autologous Tumor Infiltrating Lymphocytes (TIL or LN-145) in Patients With Metastatic Non-Small-Cell Lung Cancer

To evaluate the efficacy of LN-145 as determined by objective response rate (ORR) in patients with metastatic NSCLC using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as assessed by central review for Cohorts 1 and 2 and by the investigator for Cohorts 3, 4 and the Retreatment Cohort

To evaluate the efficacy of LN-145 as determined by objective response rate (ORR) per RECIST v1.1, as assessed by the Investigator for Cohorts 1 and 2

To evaluate efficacy parameters such as Complete Response Rate (CRR) per RECIST v1.1

To evaluate efficacy parameters such as Duration of Response (DOR) rate per RECIST v1.1

To evaluate efficacy parameters such as Disease Control Rate (DCR) per RECIST v1.1

To evaluate efficacy parameters such as Progression-Free Survival (PFS) per RECIST v1.1

To evaluate efficacy parameters such as Overall Survival (OS)

To characterize the safety profile of LN-145 in patients with non-small-cell lung cancer (NSCLC)

To determine the feasibility of generating LN-145 using tumor tissue obtained via image-guided core biopsy

Iovance Biotherapeutics, Inc.

* Dose escalation design in which administered dose levels of IMSA101 as monotherapy will be escalated stepwise in successive cohorts of 3 to 6 patients per dose group (using a standard 3+3 study design) of IMSA101 until the RP2D or maximum tolerated dose (MTD) level is identified.
* The first patient enrolled in each dose level must complete the first two weeks of Cycle 1 prior to enrolling the second and third patients.
* Dose levels to be evaluated include (although not necessarily limited to) 100 µg (representing 1/60th of the pre-clinical Highest Non-Severely Toxic Dose \[HNSTD\] dose), 200 µg, 400 µg, 800 µg, and 1,200 µg.

* Ph I combination dosing of IMSA101 shall be evaluated upon satisfaction of the following criteria:

  * A given dose level (combo dose level 1) has been confirmed as safe for monotherapy dosing (i.e. 2/6 patients experience Cycle 1 DLT).
  * The next higher dose level (combo dose level 2) has been confirmed as safe for monotherapy dosing (i.e. 2/6 patients experience Cycle 1 DLT).
  * The dose level (combo dose level 1) is found to demonstrate adequate IMSA101 pharmacodynamic (PD) activity based on exploratory endpoints.
* Eligible patients shall have demonstrated RECIST stable disease through ≥ 4 consecutive cycles of an approved PD-1/PD-L1-targeted ICI with no Grade ≥ 3 CTCAE events considered to be drug-related.
* Safety evaluations and dose escalation of IMSA101 administered in combination with current therapy shall proceed in a manner consistent with monotherapy escalation and shall proceed independently of monotherapy dose escalation.

* This dose-expansion arm of 20 patients is intended to confirm the tolerability of the RP2D and identify provocative signals of IMSA101 anti-tumor activity when administered as monotherapy
* Tumor type to be evaluated will be identified prior to Phase IIA commencement and will be documented in a protocol amendment.

* This dose-expansion arm of 20 patients is intended to confirm the tolerability of the RP2D and identify provocative signals of IMSA101 anti-tumor activity when administered as combination therapy with PD-1/PD-L1 targeted immune checkpoint inhibitors.
* This arm shall include a safety run-in of 5-10 patients.
* Tumor type and corresponding treatment combination will be identified prior to Phase IIA commencement and documented in a protocol amendment.

* This dose-expansion arm of 20 patients is intended to confirm the tolerability of the RP2D and identify provocative signals of IMSA101 anti-tumor activity when administered as combination therapy with non-PD-1/PD-L1-targeted immuno-oncology (IO) drugs approved by the FDA.
* This arm shall include a safety run-in of 5-10 patients.
* Tumor type and corresponding treatment combination will be identified prior to Phase IIA commencement and documented in a protocol amendment..

IMSA101 administered by intra-tumoral (IT) injection on Day 1 of Weeks 1, 2, and 3 for Cycle 1 and on Day 1 of Weeks 1 and 3 for all subsequent cycles.

IMSA101

Immune checkpoint inhibitor (ICI)

Immuno-oncology (IO) therapy

Teresa S Mooneyham

Open-label, dose escalation (Phase I) and dose expansion (Phase IIA) study of patients receiving intra-tumoral IMSA101 alone or in combination with an immune checkpoint inhibitor (ICI) (Phase I and II)

This is an open-label, dose escalation (Phase I), and dose expansion (Phase IIA) study designed to evaluate safety and efficacy of IMSA101 alone or in combination with an ICI (Phase I and II). Therefore, the study will be conducted in 2 phases. The dose of IMSA101 in Phase IIA will be based on the monotherapy and combination Recommended Phase 2 Doses (RP2Ds) from Phase I.

The following methodology applies to all patients (unless otherwise indicated):

* Pre-treatment screening radiographic tumor assessments will be collected within 30 days prior to initial dose for all patients. Photographic assessments for cutaneously-accessible lesions will be performed as detailed in a separate photography manual.
* Treatment cycles will be 28 days in duration with lesions injected weekly on Day 1 for the first three weeks of Cycle 1 and then every 2 weeks during cycles 2 and beyond.
* A single pre-defined lesion/lesion site (longest diameter ≥ 10 mm and ≤ 35 mm) shall be injected throughout study duration, if possible. Where the original injection site is considered by the investigator to become inaccessible, a second lesion/lesion site shall be selected as a replacement and this shall be used henceforth so long as it is considered accessible. Subsequent injection sites shall be replaced when they are considered inaccessible.
* Where no remaining accessible lesions are present and where benefit of IMSA101 therapy is, in the opinion of the investigator, being derived by the patient, continued injections of IMSA101 into the vicinity of an inaccessible lesion or, in the case that a lesion can no longer be radiographically visualized, into the last known location of the non-visible lesion shall be allowed.
* Patients will be admitted to the hospital for observation overnight following IT injection with IMSA101 on Day 1 of Cycle 1. Patients will be followed throughout the study for drug tolerability and safety by collection of clinical and laboratory data, including information on adverse events (AEs) using CTCAE v5.0 criteria, serious adverse events (SAEs), DLTs, concomitant medications, vital signs, and electrocardiograms (ECGs).
* Patients will be assessed for anti-tumor efficacy based on radiographic assessments and if applicable, photographic tumor assessments, and analysis of Objective Response Rate (ORR), Time to Progression (TTP), and Progression Free Survival (PFS) using RECIST criteria (Appendix 13.2) at screening and the end (≤ 7 days) of even numbered cycles (Cycle 2, Cycle 4, etc.) after the first dosing.

Phase I includes a monotherapy arm and an immune checkpoint inhibitor (ICI) combination therapy arm Phase II includes three arms, Arm A monotherapy, Arm B immuno-oncology (IO) combination therapy, Arm C IO combination therapy

Safety and Efficacy Study of IMSA101 in Refractory Malignancies

Phase I/IIA Safety and Efficacy Study of IMSA101 in Patients With Advanced Treatment-Refractory Malignancies

Number of adverse events and dose limiting toxicities per CTCAE v 5.0

Area under the curve minimum plasma concentration

Tumor response, based on Response Evaluation Criteria in Solid Tumors (RECIST v1.1), in patients evaluable for response.

Duration of response (DOR), based on Response Evaluation Criteria in Solid Tumors (RECIST v1.1), in patients evaluable for response.

Time to tumor progression (TTP), based on Response Evaluation Criteria in Solid Tumors (RECIST v1.1), in patients evaluable for response.

Progression free survival (PFS), based on Response Evaluation Criteria in Solid Tumors (RECIST v1.1), in patients evaluable for response.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Stereotactic Body Radiotherapy Combined With Cadonilimab for Advanced Refractory Malignant Solid Tumors	NCT05915481	Advanced Solid ... Stereotactic Bo... Immune Checkpoi... Safety Efficacy	Cadonilimab Stereotactic bo...	18 Years - 75 Years	Peking University Third Hospital
Autologous LN-145 in Patients With Metastatic Non-Small-Cell Lung Cancer	NCT04614103	Metastatic Non ...	LN-145 LN-145	18 Years - 70 Years	Iovance Biotherapeutics, Inc.
Safety and Efficacy Study of IMSA101 in Refractory Malignancies	NCT04020185	Solid Tumor, Ad...	IMSA101 Immune checkpoi... Immuno-oncology...	18 Years -	ImmuneSensor Therapeutics Inc.
Stereotactic Body Radiotherapy Combined With Cadonilimab for Advanced Refractory Malignant Solid Tumors	NCT05915481	Advanced Solid ... Stereotactic Bo... Immune Checkpoi... Safety Efficacy	Cadonilimab Stereotactic bo...	18 Years - 75 Years	Peking University Third Hospital
Stereotactic Body Radiotherapy Combined With Cadonilimab for Advanced Refractory Malignant Solid Tumors	NCT05915481	Advanced Solid ... Stereotactic Bo... Immune Checkpoi... Safety Efficacy	Cadonilimab Stereotactic bo...	18 Years - 75 Years	Peking University Third Hospital
Safety and Efficacy Study of IMSA101 in Refractory Malignancies	NCT04020185	Solid Tumor, Ad...	IMSA101 Immune checkpoi... Immuno-oncology...	18 Years -	ImmuneSensor Therapeutics Inc.

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