Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Immune System Diseases

Prostatic Neoplasms

Recurrence

Hypersensitivity

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Antineoplastic Agents

Androgens

Molgramostim

Sargramostim

Vaccines

Immunomodulating Agents

Subjects received infusion of Sipuleucel-T, at 2-week intervals, for a total of 3 infusions.

Subjects received infusion of control (autologous cellular product consisting of antigen presenting cells (APCs) prepared in the absence of PA2024 antigen) at 2-week intervals, for a total of 3 infusions.

Autologous cellular product consisting of antigen presenting cells (APCs) prepared in the absence of PA2024 antigen.

Control

Sipuleucel-T is an autologous cellular product consisting of antigen presenting cells (APCs) activated with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).

Sipuleucel-T

Robert Israel, MD

The PROTECT-PROvenge Treatment and Early Cancer Treatment trial was a Phase III trial for patients with hormone sensitive prostate cancer. The study was conducted at over 15 participating centers throughout the US. The purpose of the study was to determine if sipuleucel-T was effective for treatment of early stage, non-metastatic prostate cancer. The study compared the active vaccine to control to determine whether the product delayed the time until cancer progression.

This was a prospective, double blind, controlled, randomized trial of immunotherapy with prostatic acid phosphatase (PAP)-loaded autologous antigen presenting cells (APCs), in subjects with non metastatic prostate cancer. Subjects that qualified for this study were men who had previously undergone a prostatectomy and whose only sign of disease recurrence was a rise in serum prostate specific antigen (PSA).

The primary objectives were to compare the time to biochemical failure (BF, PSA greater than or equal to 3 ng/mL) between sipuleucel-T (treatment group) and control, and to study the safety of sipuleucel-T.

Following short-term open-label treatment with a luteinizing hormone-releasing hormone-analogue (LHRH-a), Subjects completed a checklist designed to compare androgen suppression-related side effects during periods with and without androgen suppression.

Subjects who achieved a PSA of \< 1 ng/ml were randomized to blinded treatment assignments of either sipuleucel-T or control in a 2:1 ratio. Following randomization, subjects underwent 3 leukapheresis procedures on alternate weeks (Weeks 0, 2, and 4). Approximately three days following each leukapheresis procedure, subjects received an infusion of either sipuleucel-T or control.

At the time BF was confirmed, subjects were eligible for a booster infusion. The booster process consisted of 1 leukapheresis procedure followed by 1 infusion of sipuleucel-T. The booster process, in effect under protocol amendment 5, differed from the previous booster process that consisted of 1 infusion of the same treatment assigned at randomization (sipuleucel-T or control).

Subjects continued to be observed until DF was confirmed by bone scan or computed tomography (CT) scan, or other imaging modalities as clinically indicated. After confirmed DF, subjects were followed by telephone every 6 months for safety and survival, treatment-related AEs, any CVEs, or new therapies for prostate cancer.

PROvenge Treatment and Early Cancer Treatment

Autologous PAP-loaded Dendritic Cell Vaccine (Sipuleucel-T, APC8015, Provenge®) in Patients With Non-metastatic Prostate Cancer Who Experience PSA Elevation Following Radical Prostatectomy: a Randomized, Controlled, Double-blind Trial

Time to Biochemical Failure (TTBF) was the pre-specified primary endpoint of this trial. The biochemical failure threshold was based on evidence that prostate specific antigen (PSA) had become ≥ 3 ng/mL

time to biochemical Failure (TTBF) was the pre-scpecified primary endpoint of this trial. The biochemical failure threshold was based on evidence that prostate specific antigen (PSA) had become ≥ 3 ng/mL.

Dendreon

Provenge

Provenge: Biologic: autologous cellular product consisting of antigen presenting cells (APCs) activated with PA2024, a recombinant fusion protein composed of PAP, linked to GM-CSF

Control

Control: Autologous cellular product consisting of antigen presenting cells (APCs) prepared in the absence of PA2024 antigen

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

ECOG 0=Fully Active; No restrictions.

ECOG 1= Restricted Strenuous Activity

ECOG Missing

ECOG Performance Status is a method used to assess the functional status of a patient. The scale ranges from 0-5. 0=Fully active, able to carry on all pre-disease performance without restriction; 1=Restricted in physically strenuous activity but ambulatory and able to carry out light or sedentary work; 2=Ambulatory, capable of all self-care but unable to carry out work activities. Up and about \>50% of waking hour; 3=Capable of limited self-care, confined to bed or chair \>50% of waking hours; 4=Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; 5=Dead

Eastern Cooperative Oncology Group (ECOG) Performance Status

Weight

Gleason Score ≤ 6

Gleason Score =7

Gleason Score ≥ 8

Gleason score= prostate cancer grading system based on how tissue looks under a microscope. Scores range 2-10 and indicates how likely it is that a tumor will spread. A low score means the cancer tissue is similar to normal tissue and the tumor is less likely to spread. Gleason Score ≤ 6=the tumor is well differentiated, less aggressive and likely to grow more slowly;7=the tumor is moderately differentiated, moderately aggressive, and likely to grow but may not spread quickly;≥8=the tumor is poorly differentiated or undifferentiated, highly aggressive, and likely to grow faster and spread.

Gleason Score

Time from diagnosis to randomization

Shabnam Vaziri

25th Cumulative Incidence Percentile

50th Cumulative Incidence Percentile

75th Cumulative Incidence Percentile

Number of subjects that met biochemical failure criteria.

Time to Biochemical Failure Cumulative Incidence Percentile

Number of Subjects That Met Biochemical Failure Status

Treatment Phase 1

Surveillance Phase

Long-term Follow-up

Respiratory Tract (Lung and Bronchial) Diseases

Behaviors and Mental Disorders

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Disease Progression

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Quality of Life

Micronutrients

Hematinics

Vitamins

Immune Checkpoint Inhibitors

Pemetrexed

Docetaxel

Tubulin Modulators

Antimitotic Agents

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

OSE2101 was administered as a 1 mL-subcutaneous injection on Day 1 every three weeks for six cycles, then every eight weeks for the remainder of year one and finally every twelve weeks beyond year one until unequivocal RECIST 1.1-defined disease progression as determined by the investigator, unacceptable toxicity, or consent withdrawal. Should pseudo progression or delayed response to treatment suspected in arm A, investigator may continue treatment beyond the time of RECIST-defined progression, if the patient is perceived to be experiencing clinical benefit of OSE2101. OSE2101 dose was 5 mg of peptides (0.5 mg for each peptide).

Patients receiving docetaxel: Docetaxel 75 mg/m2 will be administered by intravenous infusion over 1 hour on Day 1 of a 21-day cycle.

Patients receiving pemetrexed: Pemetrexed, 500 mg/m2, will be administered by intravenous infusion over 10 minutes on Day 1 of a 21-day cycle.

Docetaxel and pemetrexed will be continued until unequivocal RECIST 1.1-defined disease progression as determined by the investigator, unacceptable toxicity, or consent withdrawal.

OSE2101

Dominique Costantini, Dr

The aim of this clinical trial was to determine if the therapeutic cancer vaccine OSE2101 (TEDOPI) was more effective than standard chemotherapy (docetaxel or pemetrexed) in treating HLA-A2 positive patients with metastatic NSCLC who progressed after sequential or concurrent chemotherapy and immune checkpoint inhibitor given in first or second-line treatment.

The main questions were to compare the survival, the tolerance to treatment and the quality of life of patients between the two arms of treatment (OSE2101 versus standard chemotherapy)

The study was a two-step randomized (2:1) study. Patients were stratified by histology (non-squamous versus squamous), best response to first-line treatment \[complete response or partial response versus stable disease or progressive disease\] and line of treatment with prior ICI (first-line ICI when combined with platinum-based chemotherapy versus second-line ICI when administered as sequential treatment). Primary endpoint was overall survival (OS). Interim OS futility analysis was planned as per Fleming design. In April 2020 at the time of the interim analysis, a decision was taken to early stop the accrual due to COVID-19 after 219 out of 363 patients were randomized. It led to a decrease of the study power from 80% to 62%. At the time of the interim analysis, a subgroup of patients was identified from stratification factor based on a clinical and biological rationale: those who received ICI second line and having received at least 12 weeks ICI. This subgroup was defined as ICI secondary resistance. The final analysis was carried out in the subgroup of patients with ICI secondary resistance and in all patients (ICI primary and secondary resistance).

Two-step open-label study with a planned interim OS futility in experimental arm per Fleming design (Step1) Central randomisation (2:1) with stratification by histology (non-squamous versus squamous), best response to first-line treatment \[complete response (CR) or partial response (PR) versus stable disease (SD) or PD\] and line of prior anti-PD(L)1 treatment (first-line when combined with platinum-based chemotherapy versus second-line when administered as sequential treatment after first-line platinum-based chemotherapy).

OSE2101 Versus Chemotherapy in HLA-A2 Positive Patients With Advanced NSCLC After Immune Checkpoint Inhibitor Failure

A Randomized Phase III Trial of OSE2101 Compared With Chemotherapy (Docetaxel or Pemetrexed) in HLA-A2 Positive Patients With Advanced Non-Small Cell Lung Cancer With Progressive Disease After Immune Checkpoint Inhibitors

The supporting information as Study Protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR) may be shared with other researchers if OSE Immunotherapeutics agreed and after signature of a confidential agreement between the parties

Objective Response rate (OOR) was defined as number of patients with Complete Response (CR) + Partial Response (PR) assessed by investigator per "Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions based on CT scan in patients with ICI secondary resistance. Complete Response (CR) defined as disappearance of all target lesions; Partial Response (PR) as \>=30% decrease in the sum of the longest diameter of target lesions. Investigator-assessed ORR was an exploratory endpoint as not relevant as primary, nor secondary endpoints to evaluate a cancer vaccine.

Duration of Objective Response (OOR) was defined as number of patients with Complete Response (CR) or Partial Response (PR) at 6 months assessed by investigator per "Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions based on CT scan in patients with ICI secondary resistance. Complete Response (CR) defined as disappearance of all target lesions; Partial Response (PR) as \>=30% decrease in the sum of the longest diameter of target lesions

Time to next lung cancer therapy was defined as the time from randomisation to the date of initiation of the first lung cancer therapy during the survival follow-up form

OS defined as the time from randomisation to death from any cause in patients with ICI secondary resistance

Post-progression survival was defined as the time from the earliest date of progression according to RECIST 1.1 until death in patients with ICI secondary resistance

Time to Worsening ECOG PS was defined as the time from randomization to the earliest date when ECOG PS was \>1 in patients with ICI secondary resistance. Time to worsening ECPG PS was summarized by treatment arm using the Kaplan-Meier method. The median event time for each treatment arm and the corresponding 2-sided 95% confidence interval were provided. By protocol, ECOG PS was not collected when a patient permanenetly discontinued the study treatment. Patients without ECOG PS worsening were censored at the last time when an ECOG value was recorded.

Mean change from baseline to treatment discontinuation in Quality of Life (QoL) score of the following functional subscales analyzed separately: global health status, physical, role, cognitive, emotional and social functioning. Each score range from 0 to 100 after normalisation. Highest scores correspond to a better quality of life. The mean score change was assessed using a mixed-effects model for repeated measures analysis with the patient as the random effect, treatment, visit and treatment-by-visit interaction as explanatory variables and baseline score as covariates. If the mean score change is negative, it means a deterioration of QoL. If the mean score change is positive or 0, it means an improvement or stability of QoL

Mean change from baseline to treatment discontinuation in Quality of Life (QoL) score of the following symptoms subscales analyzed separately: Fatigue, Constipation, Dyspnea, Nausea and Vomiting, Pain, Insomnia, Appetite loss, Diarrhea, Financial Difficulties. Each score range from 0 to 100 after normalisation. Lowest scores correspond to a better QoL. The mean score change was assessed using a mixed-effects model for repeated measures analysis with the patient as the random effect, treatment, visit and treatment-by-visit interaction as explanatory variables and baseline score as covariates. If the mean score change is negative, it means a deterioration of QoL. If the mean score change is positive or 0, it means an improvement or stability of QoL.

Mean change from baseline to treatment discontinuation in Quality of Life (QoL) score of the following symptoms subscales analyzed separately: Alopecia, Peripheral Neuropathy, Sore mouth, Dysphagia, Dyspnea, Pain in arm or shoulder, Pain in chest, Pain in other parts, Hemoptysis, Coughing. Each score range from 0 to 100 after normalisation. Lowest scores correspond to a better QoL. The mean score change was assessed using a mixed-effects model for repeated measures analysis with the patient as the random effect, treatment, visit and treatment-by-visit interaction as explanatory variables and baseline score as covariates. If the mean score change is negative, it means a deterioration of QoL. If the mean score change is positive or 0, it means an improvement or stability of QoL.

DCR at 6 months defined as the number of patients with Complete Response (CR), Partial Response (PR) or Stable Disease (SD) assessed by investigator per "Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions based on CT scan in patients with ICI secondary resistance. Complete Response (CR) defined as disappearance of all target lesions; Partial Response (PR) as \>=30% decrease in the sum of the longest diameter of target lesions; Stable disease (SD) defined as neither sufficient shrinkage (compared to baseline) to qualify for CR or PR nor sufficient increase (taking as reference the smallest sum of diameters at baseline or while on study, whichever is smallest) to qualify for progressive disease (PD) (e.g. decrease of the sum of the longest diameters of target lesions \<30% or increase up to 20%)

PFS was defined as the time from randomization to the earliest date of progression assessed by investigator per "Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions based on CT scan in patients with ICI secondary resistance. Progressive disease (PD) defined as increase of target lesions \>=20% taking as reference the smallest sum of diameters at baseline or while on study, whichever is smallest)

OSE Immunotherapeutics

A total of 7 patients did not receive the study treatment (n=1 in OSE2101 arm, n=6 in docetaxel or pemetrexed arm).

Subcutaneous injection at 5 mg, 1 ml every 3 weeks for 6 cycles, then every 8 weeks until 1 year of treatment and thereafter every 12 weeks

Docetaxel by intravenous infusion over 1 hour at 75 mg/m2 every 3 weeks Pemetrexed by intravenous infusion over 10 minutes at 500 mg/m2 every 3 weeks both with premedication according to international guidelines

Docetaxel or Pemetrexed

All randomized patients with ICI primary and secondary resistance

Primary efficacy analysis was carried out in the subgroup of patients with ICI secondary resistance defined as as disease progression after ICI second line \> or equal to 12 weeks identified from the stratification factor (previous line of ICI). Safety analysis was done in all patients.

Age, Categorical

Final analysis was carried out in the subgroup of patients with ICI secondary resistance defined as as disease progression after ICI second line \> or equal to 12 weeks identified from the stratification factor (previous line of ICI)

All patients with ICI primary and secondary resistance

Primary efficacy analysis was carried out in the subgroup of patients with ICI secondary resistance defined as as disease progression after ICI second line \> or equal to 12 weeks identified from the stratification factor (previous line of ICI)/ Safety analysis was done in all patients

Missing data in 11 patients (n=9 in OSE2101 arm, n=2 in docetaxel or pemetrexed arm)

Race/Ethnicity, Customized

Czechia

Poland

Italy

Israel

France

Germany

Spain

Hungary

219 HLA-A2 positive patients with advanced NSCLC who progressed after sequential or concurrent chemotherapy and Immune Checkpoint Inhibitor (either primary or secondary resistance) were randomized. Safety analysis was done in overall population. Primary efficacy analysis was carried out from stratification factor in subgroup of patients with ICI secondary resistance (who had a disease progression after ICI second line \> or equal to 12 weeks)

In April 2020 at time of planned interim analysis, decision was taken to prematurely stop the accrual due to COVID-19. Early termination led to small numbers of subject analyzed. The statistical plan was revised to propose the primary efficacy analysis in subgroup of patients with ICI secondary resistance (defined as progression after ICI second line \>= to 12 weeks from stratification criteria based on biological and clinical rationale).

Chief Medical Officer Immuno-Oncology

OS in the ITT population with ICI resistance (primary and secondary resistance)

OS analysis in patients with ICI secondary resistance defined as disease progression after ICI second line \> or equal to 12 weeks (n=118) OS analysis in the ITT population with ICI resistance (primary and secondary resistance) is described in statistical analysis 2 (n=219)

Overall Survival (OS)

Post-progression survival in patients with ICI secondary resistance

Post-progression survival in ITT population with ICI resistance (primary and secondary)

Patients with ICI secondary resistance defined as disease progression after ICI second line \> or equal to 12 weeks (n=118)

Post-Progression Survival

Time to worsening ECOG PS \>1 in patients with ICI secondary resistance

Time to worsening ECOG PS in the ITT population with ICI resistance (primary and secondary)

Time to Worsening ECOG PS

QLQ C30 Global Health Status in Patients with ICI secondary resistance

QLQ-C30 Physical functioning in patients with ICI secondary resistance

QLQ-C30 Role functioning in patients with ICI secondary resistance

QLQ-C30 Emotional functioning in patients with ICI secondary resistance

QLQ-C30 Cognitive functioning in patients with ICI secondary resistance

Global Health Status

Physical functioning

Role functioning

Emotional functioning

Cognitive functioning

Social funtioning

Mean Changes in Functional Subscales of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) From Baseline to Treatment Discontinuation in Patients With ICI Secondary Resistance

QLQ-C30 Fatigue in ICI secondary resistance

QLQ-C30 Constipation in ICI secondary resistance

QLQ-C30 Dyspnea in ICI secondary resistance

QLQ-C30 Nausea and Vomiting in ICI secondary resistance

QLQ-C30 Insomnia in ICI secondary resistance

QLQ-C30 Appetite loss in ICI secondary resistance

QLQ-C30 Diarrhea in ICI secondary resistance

QLQ-C30 Financial difficulties in ICI secondary resistance

Fatigue

Constipation

Dyspnea

Nausea and Vomiting

Pain

Insomnia

Appetite loss

Diarrhea

Financial difficulties

QLQ-C30 Symptoms score changes from baseline in patients with ICI secondary resistance

Mean Changes in Symptoms Subscales of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) From Baseline to Treatment Discontinuation in Patients With ICI Secondary Resistance

QLQ-LC13 Alopecia in ICI secondary resistance

QLQ-LC 13 Peripheral neuropathy in ICI secondary resistance

QLQ-LC13 Sore mouth in ICI secondary resistance

QLQ-LC13 Dysphagia in ICI secondary resistance

QLQ-LC13 Pain in chest in ICI secondary resistance

QLQ-LC 13 Hemoptysis in ICI secondary resistance

QLQ-LC13 Coughing in ICI secondary resistance

Alopecia

Peripheral neuropathy

Sore mouth

Dysphagia

Pain in arm or shoulder

Pain in chest

Pain in other parts

Hemoptysis

Coughing

QLQ-LC 13 symptoms score changes from baseline in patients with ICI secondary resistance

Mean Changes in Symptoms Subscales of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Lung Cancer (QLQ-LC13) From Baseline to Treatment Discontinuation in Patients With ICI Secondary Resistance

DCR at 6 months in patients with ICI secondary resistance

DCR at 6 months in ITT patients with ICI resistance (primary and secondary)

116 out of 118 patients had measurable lesions per RECIST 1.1 at baseline (n=78/80 in OSE2101 arm, 38/38 in docetaxel or pemetrexed arm). One patient had no post-baseline RECIST 1.1 assessement (n=1 in OSE2101 arm).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PROvenge Treatment and Early Cancer Treatment	NCT00779402	Prostate Cancer	Control Sipuleucel-T	18 Years - 80 Years	Dendreon
OSE2101 Versus Chemotherapy in HLA-A2 Positive Patients With Advanced NSCLC After Immune Checkpoint Inhibitor Failure	NCT02654587	Non Small Cell ...	OSE2101 Docetaxel Pemetrexed	18 Years -	OSE Immunotherapeutics
Sequencing of Sipuleucel-T and ADT in Men With Non-metastatic Prostate Cancer	NCT01431391	Prostatic Neopl... Prostate Cancer Prostatic Adeno...	sipuleucel-T leuprolide acet...	18 Years -	Dendreon
Provenge® (Sipuleucel-T) Active Cellular Immunotherapy Treatment of Metastatic Prostate Cancer After Failing Hormone Therapy	NCT00065442	Prostate Cancer	Sipuleucel-T APC-Placebo	18 Years -	Dendreon

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