Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Analgesics

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Immunologic Factors

Immunosuppressive Agents

Interleukin-2

Mesna

Phase 1 dose escalation will utilize a 3+3 dose escalation design and will evaluate safety, feasibility, and preliminary efficacy of four cohort dose levels of CYNK-001 administered after a 6M IU subcutaneous dose of rhIL-2 for both IV and IC cycles. Up to 21 patients will be enrolled over 4 dosing cohorts in Phase 1.

To evaluate efficacy and safety of CYNK-001 administrations in recurrent GBM at maximum tolerated dose for IV and IC per Phase 1 outcome. No patients staggering will be implemented in phase 2a. DMC will review the phase 2a entirely

Phase 1 Lymphodepletion Days -5,-4 and -3 Cyclophosphamide 900 mg/m2, Fludarabine 30 mg/m2 and Mesna per SOC

IL 2 at 6M IU subcutaneous administration:

For IV cycle ( cycle1) rhIL2 will be administered on Days 1,3,5,8,9,11 and 15 . On days 1, 8 and 15 rhIL-2 will be administered 1 to 3 hours prior to CYNK-001 infusions For IC cycles rhIL2 will be administered 1 to 3 hours prior to each CYNK-001 IC dose.

CYNK-001 : for IV at 2.4 x10\^9 or 3.6 x10\^9 cells Days 1,8 and 15

Tumor resection will take place 7 to 14 day follow by first IC cycle ( Cycle 2) at 100 Million cells or 200 Million cells

IC cycles 3,4,5 once a week for three weeks , 28 days cycle at100 Million cells or 200 Million cells only for Phase 1 cohort 4 and Phase 2a

CYNK-001 systemic and Intra cavity administration

Adrian Kilcoyne, MD

A Phase 1/2a Open Label Multicenter, Non-Randomized, Trial to Assess the Safety and Efficacy of CYNK-001 in Combination with Recombinant Human Interleukin-2 in Adults with Recurrent Resection Eligible IDH1 wild-type Glioblastoma. For phase I portion, the study objectives to assess the safety and feasibility CYNK-001 in combination with rhIL2 of Intravenous (IV) infusion and Intracavitary (IC) administrations following tumor resection and to establish a maximum tolerated dose (MTD) and a Recommended Phase 2a Dose (RP2D) for IV and IC CYNK-001 administration. For Phase IIa, to evaluate efficacy and safety of CYNK-001 administrations in recurrent GBM as measured by Progression Free Survival at 6 months (PFS6M)

The study will contain two phases for the following objectives •The Phase 1 Dose Escalation will utilize a 3+3 dose escalation design and will evaluate safety, feasibility, and preliminary efficacy of four cohort dose levels of CYNK-001 administered after a 6M IU subcutaneous dose of rhIL-2 for both IV and IC cycles. Up to 21 patients will be enrolled over 4 dosing cohorts in Phase1 and 45 patients enrolled for phase IIa. Cohort 4 will be the safety run for Phase IIa. Cohort 4 in its entirety will be reviewed by the DMC prior to starting Phase 2a portion of this study. Phase 2a will continue to explore efficacy and safety of CYNK-001 in combination with rhIL2 in patients with recurrent resection eligible IDH1 wild-type glioblastoma.

CYNK-001 IV and IC in Combination With IL2 in Surgical Eligible Recurrent GBM With IDH-1 Wild Type

A Phase I/IIa Open Label Multicenter, Non-Randomized, Trial to Assess the Safety and Efficacy of CYNK-001in Combination With Recombinant Human Interleukin-2 in Adults With Recurrent Resection Eligible IDH1 Wild-type Glioblastoma

is defined as the time from the tumor resection until the date of death 9 and 12 months (PFS9 and PFS12) post tumor resection

is defined as the median 95% CIs time from the tumor resection until the date of death 9 and 12 months (PFS9 and PFS12) post tumor resection

is defined as the median as the 95%CI time from the tumor resection until the date of death.

is defined as the time from the tumor resection to the date of first documented disease progression determined in accordance with RANO(iRANO).

Defined as the proportion of subjects with best overall response of either complete response (CR) or partial response (PR)

To assess patient quality of life at baseline and post tumor resection surgery per the schedule of Events using EORTC QLQ C30 and EORTC QLQ BN 20 scale

NANO scale provides an objective clinician-reported outcome of neurologic function with high inter-observer agreement

any event not present prior to the initiation of the drug treatment

any untoward or unfavorable medical occurrence in patient during the clinical trial

Defined as the maximum dose safely administered intravenously or Intracavitary for the treatment of patients with GBM

Defined as the number of patients experience Adverse Events and severity

To evaluate CYNK-001 efficacy post tumor resection and survival within PFS6 Month

is defined as the time from the tumor resection to the date of first documented disease progression determined in accordance with RANO (and iRANO) or death due to any reason, whichever occurs first

is defined as the time from the tumor resection until the date of death at 6,9 and 12 months

Celularity Incorporated

Blood and Lymph Conditions

Immune System Diseases

Infections

Behaviors and Mental Disorders

Lymphoma

Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Epstein-Barr Virus Infections

Virus Diseases

Aggression

Lymphoma, Extranodal NK-T-Cell

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Peripheral T-cell Lymphoma

Extranodal Nasal NK/T Cell Lymphoma

Immunomodulating Agents

Treatment consists of 2 infusions of 2x10E7 cells/m2 given on Days 1 and 15 intravenously via a peripheral or central line over a 1 to 10 minute period.

Subjects who tolerate the study treatment well and who do not require treatment with an alternative chemotherapeutic agent will be eligible for up to 3 additional infusions of 2x10E7 cells/m2 administered at week 8, month 3 and month 6.

baltaleucel-T

Helen Heslop, MD

Kurt Gunter, MD

To investigate the efficacy of autologous EBV-specific T-cells for the treatment of patients with aggressive EBV positive extranodal NK/T-cell lymphoma

Cellular Immunotherapy Treatment Antigen-Directed for EBV Lymphoma

A Phase 2 Single Arm Study to Investigate the Efficacy of Autologous EBV-specific T-cells for the Treatment of Patients With Aggressive EBV Positive Extranodal NK/T-cell Lymphoma (ENKTCL)

Defined as best observed response (complete response or partial response) per Lugano 2014 Disease Response Criteria.

Cell Medica Ltd

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Laryngeal Diseases

Neoplasms, Squamous Cell

Immune Checkpoint Inhibitors

Cetuximab

Antineoplastic Agents, Immunological

Participants will receive intravenous (IV) monalizumab 750 mg every two weeks (Q2W) and IV cetuximab 400 mg/m\^2 initial dose followed by 250 mg/m\^2 every one week (Q1W) until disease progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Participants will receieve IV placebo matched to monalizumab Q2W and IV cetuximab 400 mg/m\^2 initial dose followed by 250 mg/m\^2 Q1W until disease progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Participants will receive IV infusion of monalizumab as stated in arm description.

Monalizumab

Participants will receive IV infusion of cetuximab as stated in arm description.

Participants will receive IV infusion of placebo as stated in arm description.

Placebo

Roger B Cohen, MD

Jérôme Fayette, MD

Dario Ruscica, MD

This is a randomized, double-blind, multicenter, global Phase 3 study to assess the efficacy and safety of monalizumab and cetuximab, compared to placebo and cetuximab, in Participants with recurrent or metastatic head and neck cancer.

Participants with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) who had prior immune checkpoint inhibitor and platinum-based chemotherapy treatment will be randomized in a 2:1 ratio to monalizumab and cetuximab or placebo and cetuximab. Efficacy and safety assessments will be performed periodically from the time of enrollment and throughout the study. Participants in all arms will continue therapy until progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. All Participants will be followed for survival after progression is confirmed.

Parallel study. Participants will be randomized in a 2:1 ratio to monalizumab and cetuximab or placebo and cetuximab.

Assessment of Efficacy and Safety of Monalizumab Plus Cetuximab Compared to Placebo Plus Cetuximab in Recurrent or Metastatic Head and Neck Cancer

A Phase 3 Randomized, Double-blind, Multicenter, Global Study of Monalizumab or Placebo in Combination With Cetuximab in Participants With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Previously Treated With an Immune Checkpoint Inhibitor

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

The OS is defined as time from the date of randomization until death due to any cause regardless of whether the participant withdraws from randomized therapy or receives another anti-cancer therapy (i.e. date of death or censoring - date of randomization + 1). The OS was analyzed using Kaplan-Meier technique. Statistical analysis was performed using P-value from a stratified log-rank test and hazard ratio (HR) and confidence intervals (CIs) from a stratified Cox proportional hazards model. Analyses were stratified on World Health Organization/ Eastern Cooperative Oncology Group performance status (WHO/ECOG PS) (0 or 1) and number of prior lines of therapy in recurrent or metastatic (R/M) setting (1 or 2).

The OS is defined as time from the date of randomization until death due to any cause regardless of whether the participant withdraws from randomized therapy or receives another anti-cancer therapy (i.e. date of death or censoring - date of randomization + 1). The OS was analyzed using Kaplan-Meier technique. Statistical analysis was performed using P-value from a stratified log-rank test and HR and CIs from a stratified Cox proportional hazards model. Analyses were stratified on HPV status (OPC HPV positive or HPV-unrelated), WHO/ECOG PS (0 or 1) and number of prior lines of therapy in R/M setting (1 or 2).

PFS per RECIST 1.1 as assessed by the investigator is defined as time from randomization until date of RECIST 1.1-defined radiological progressive disease (PD) or death regardless of whether participant withdraws from therapy or received subsequent anticancer therapy prior to progression. PD: at least 20% increase in sum of diameters of target lesions (TLs), taking as reference the smallest sum on study (nadir) and sum must demonstrate an absolute increase of at least 5 mm from nadir or unequivocal progression of existing non-TLs (NTLs) or appearance of new lesions. PFS was analyzed using Kaplan-Meier technique. Statistical analysis was performed using P-value from stratified log-rank test and HR and CIs from a stratified Cox proportional hazards model. Analyses were stratified on WHO/ECOG PS (0/1) and no. of prior lines of therapy in R/M setting.

PFS per RECIST 1.1 as assessed by the investigator is defined as time from randomization until date of RECIST 1.1-defined radiological progressive disease (PD) or death regardless of whether participant withdraws from therapy or received subsequent anticancer therapy prior to progression. PD: at least 20% increase in sum of diameters of target lesions (TLs), taking as reference the smallest sum on study (nadir) and sum must demonstrate an absolute increase of at least 5 mm from nadir or unequivocal progression of existing NTLs or appearance of new lesions. PFS was analyzed using Kaplan-Meier technique. Statistical analysis was performed using P-value from a stratified log-rank test and HR and CIs from a stratified Cox proportional hazards model. Analyses were stratified on HPV status, WHO/ECOG PS (0/1) and no. of prior lines of therapy in R/M setting.

The OR is defined as the percentage of participants with at least one confirmed investigator-assessed response of complete response (CR) or partial response (PR) as assessed by RECIST 1.1 guidelines. The CR is defined as disappearance of all TLs and NTLs, any pathological lymph nodes (target and non-target) must have reduction in short axis \< 10 mm, and no new lesions. The PR is defined as at least a 30% decrease in the sum of the diameters (SoD) of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. Percentage of participants with OR is reported. Participants who had measurable disease at baseline per the site investigator were analyzed for this outcome.

The OR is defined as the percentage of participants with at least one confirmed investigator-assessed response of CR or PR as assessed by RECIST 1.1 guidelines. The CR is defined as disappearance of all TLs and NTLs, any pathological lymph nodes (target and non-target) must have reduction in short axis \< 10 mm, and no new lesions. The PR is defined as at least a 30% decrease in the SoD of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. Percentage of participants with OR is reported. Participants who had measurable disease at baseline per the site investigator were analyzed for this outcome.

The DoR is defined as the time from the date of first documented confirmed response until date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). The CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The PR is defined as at least a 30% decrease in the SoDs of TLs (compared to baseline) and no new lesions. Confirmation of CR and PR is required by a repeat, consecutive assessment no less than 4 weeks from the date of first documentation. The PD is defined as at least a 20% increase in the SoDs of TLs, taking as reference the smallest previous SoDs (nadir) and the sum must demonstrate an absolute increase of at least 5 mm from nadir or unequivocal progression of existing NTLs or appearance of new lesions. The DoR was analyzed using Kaplan-Meier technique.

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs included events from the first dose of study drug, up to 90 days after the last dose of study drug received or up to the start date of any subsequent anticancer therapy following discontinuation of study drug, or the final safety DCO date of 01Sep2022, whichever occurred first.

Participants with abnormal laboratory parameters reported as TEAEs are reported. Laboratory analysis included hematology and clinical chemistry. TEAEs included events from the first dose of study drug, up to 90 days after the last dose of study drug received or up to the start date of any subsequent anticancer therapy following discontinuation of study drug, or the final safety DCO date of 01Sep2022, whichever occurred first.

Participants with abnormal vital signs (heart rate, blood pressure, temperature, and respiratory rate) reported as TEAEs are reported. TEAEs included events from the first dose of study drug, up to 90 days after the last dose of study drug received or up to the start date of any subsequent anticancer therapy following discontinuation of study drug, or the final safety DCO date of 01Sep2022, whichever occurred first.

Participants with Abnormal ECGs reported as TEAEs are reported. TEAEs included events from the first dose of study drug, up to 90 days after the last dose of study drug received or up to the start date of any subsequent anticancer therapy following discontinuation of study drug, or the final safety DCO date of 01Sep2022, whichever occurred first.

Innate Pharma

AstraZeneca

All-Cause Mortality (ACM) reports data for ARP set; AE/SAE data is reported for SAS. Two participants died in follow-up period in each arm, after consent withdrawal from study, so number of deaths reported in ACM is different than of participant flow. TEAEs: Events from first dose of study drug (SD) up to 90 days after last dose of SD received or up to start date of any subsequent anticancer therapy following discontinuation of SD or final safety DCO of 01Sep22, whichever occurred first.

Participants received IV monalizumab 750 mg Q2W and IV cetuximab 400 mg/m\^2 initial dose followed by 250 mg/m\^2 Q1W until disease progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Monalizumab 750 mg Q2W + Cetuximab 400 mg/m^2

Participants receieved IV placebo matched to monalizumab Q2W and IV cetuximab 400 mg/m\^2 initial dose followed by 250 mg/m\^2 Q1W until disease progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion was met.

Placebo Q2W + Cetuximab 400 mg/m^2

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Baseline analysis population included all participants randomized up to the safety DCO date of 01Sep2022.

Study enrolment was discontinued after the planned initial interim futility analysis (IA1) due to unlikelihood of achieving statistical significance for OS in the primary endpoint (HPV-unrelated). Therefore, symptoms, function, health-related quality of life (HRQoL), European Organization for Research and Treatment of Cancer (EORTC) scale/item score, pharmacokinetic (PK) parameters, immunogenicity, human leukocyte antigen E (HLA-E), and NKp46+ expression outcomes were not evaluated.

Global Clinical Lead

The HPV-unrelated analysis set included all participants who were randomized at least 2 months before the 11May2022 DCO (i.e. on or before 11Mar2022) and were either oropharyngeal cancer (OPC) HPV negative or non OPC regardless of the HPV status.

Overall Survival (OS) in Human Papillomavirus (HPV)-Unrelated Analysis Set

The FAS included all participants randomized at least 2 months before the DCO 11May2022 (i.e. on or before 11Mar2022).

Overall Survival in Full Analysis Set (FAS)

The HPV-unrelated analysis set included all participants who were randomized at least 2 months before the 11May2022 DCO (i.e. on or before 11Mar2022) and were either OPC HPV negative or non OPC regardless of the HPV status.

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment in HPV-unrelated Analysis Set

Progression-Free Survival Per RECIST 1.1 by Investigator Assessment in FAS

The HPV-unrelated analysis set included all participants who were randomized at least 2 months before the 11May2022 DCO (i.e. on or before 11Mar2022) and were either OPC HPV negative or non OPC regardless of the HPV status. Participants who had measurable disease at baseline per the site investigator were analyzed for this outcome.

Percentage of Participants With Objective Response (OR) Per RECIST 1.1 in HPV-unrelated Analysis Set

The FAS included all participants randomized at least 2 months before the DCO 11May2022 (i.e. on or before 11Mar2022). Participants who had measurable disease at baseline per the site investigator were analyzed for this outcome.

Percentage of Participants With OR Per RECIST 1.1 in FAS

The HPV-unrelated analysis set included all participants who were randomized at least 2 months before the 11May2022 DCO (i.e. on or before 11Mar2022) and were either OPC HPV negative or non OPC regardless of the HPV status. The DoR is assessed for only those participants who had OR.

Duration of Response (DoR) Per RECIST 1.1 in HPV-unrelated Analysis Set

The FAS included all participants randomized at least 2 months before the DCO 11May2022 (i.e. on or before 11Mar2022). The DoR is assessed for only those participants who had OR.

Duration of Response Per RECIST 1.1 in FAS

The Safety Analysis Set included all participants randomized at least 2 months before the DCO 01Sep2022 (i.e. on or before 01Jul2022).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
CYNK-001 IV and IC in Combination With IL2 in Surgical Eligible Recurrent GBM With IDH-1 Wild Type	NCT05218408	Astrocytoma, Gr... Glioblastoma Giant Cell Glio... Glioblastoma Mu...	CYNK-001 system...	18 Years -	Celularity Incorporated
Cellular Immunotherapy Treatment Antigen-Directed for EBV Lymphoma	NCT01948180	Lymphoma, Extra... EBV	baltaleucel-T	18 Years -	Cell Medica Ltd
Assessment of Efficacy and Safety of Monalizumab Plus Cetuximab Compared to Placebo Plus Cetuximab in Recurrent or Metastatic Head and Neck Cancer	NCT04590963	Squamous Cell C...	Monalizumab Cetuximab Placebo	18 Years - 130 Years	AstraZeneca
Combination of Irreversible Electroporation and NK Immunotherapy for Recurrent Liver Cancer	NCT03008343	Recurrent Liver...	Irreversible El... Natural killer	30 Years - 60 Years	Fuda Cancer Hospital, Guangzhou
CYNK-001 IV and IC in Combination With IL2 in Surgical Eligible Recurrent GBM With IDH-1 Wild Type	NCT05218408	Astrocytoma, Gr... Glioblastoma Giant Cell Glio... Glioblastoma Mu...	CYNK-001 system...	18 Years -	Celularity Incorporated
Implication of CCR4-NOT Complex Subunit 7 Expression in Natural Killer Cell Resistance in Metastatic Breast Cancer	NCT06320392	Metastatic Brea...		-	Ain Shams University
Combination of Irreversible Electroporation and NK Immunotherapy for Recurrent Liver Cancer	NCT03008343	Recurrent Liver...	Irreversible El... Natural killer	30 Years - 60 Years	Fuda Cancer Hospital, Guangzhou
Cellular Immunotherapy Treatment Antigen-Directed for EBV Lymphoma	NCT01948180	Lymphoma, Extra... EBV	baltaleucel-T	18 Years -	Cell Medica Ltd
Assessment of Efficacy and Safety of Monalizumab Plus Cetuximab Compared to Placebo Plus Cetuximab in Recurrent or Metastatic Head and Neck Cancer	NCT04590963	Squamous Cell C...	Monalizumab Cetuximab Placebo	18 Years - 130 Years	AstraZeneca
Implication of CCR4-NOT Complex Subunit 7 Expression in Natural Killer Cell Resistance in Metastatic Breast Cancer	NCT06320392	Metastatic Brea...		-	Ain Shams University

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