Trial Outcomes & Findings for Safety and Efficacy of Listeria in Combination With Chemotherapy as Front-line Treatment for Malignant Pleural Mesothelioma (NCT NCT01675765)

NCT ID: NCT01675765

Last Updated: 2020-09-30

Results Overview

Count of subjects with incidences of adverse events.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

60 participants

Primary outcome timeframe

From first study dose until 28 days after the final dose (an average of 44 weeks)

Results posted on

2020-09-30

Participant Flow

Participant milestones

Participant milestones
Measure	Immunotherapy Plus Chemotherapy Weeks 1 and 3: CRS-207 (1 × 10\^9 CFU) Weeks 5, 8, 11, 14, 17 and 20 (up to 6 cycles every 21 days): pemetrexed (500 mg/m\^2) and cisplatin (75 mg/m\^2) Weeks 23 and 26: CRS-207 Maintenance Vaccinations: CRS-207 every 8 weeks (starting at Week 34) until disease progression Immunotherapy plus chemotherapy: live attenuated double deleted Lm	Immunotherapy With Cyclophosphamide Plus Chemotherapy Weeks 1 and 3: cyclophosphamide (200 mg/m\^2), CRS-207 (1 × 10\^9 CFU) Weeks 5, 8, 11, 14, 17 and 20 (up to 6 cycles every 21 days): pemetrexed (500 mg/m\^2) and cisplatin (75 mg/m\^2) Weeks 23 and 26: cyclophosphamide one day before CRS-207 Maintenance Vaccinations: cyclophosphamide one day before CRS-207 every 8 weeks (starting at Week 34) until disease progression Immunotherapy with cyclophosphamide plus chemotherapy: live attenuated double deleted Lm
Overall Study STARTED	38	22
Overall Study COMPLETED	27	14
Overall Study NOT COMPLETED	11	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Immunotherapy Plus Chemotherapy Weeks 1 and 3: CRS-207 (1 × 10\^9 CFU) Weeks 5, 8, 11, 14, 17 and 20 (up to 6 cycles every 21 days): pemetrexed (500 mg/m\^2) and cisplatin (75 mg/m\^2) Weeks 23 and 26: CRS-207 Maintenance Vaccinations: CRS-207 every 8 weeks (starting at Week 34) until disease progression Immunotherapy plus chemotherapy: live attenuated double deleted Lm	Immunotherapy With Cyclophosphamide Plus Chemotherapy Weeks 1 and 3: cyclophosphamide (200 mg/m\^2), CRS-207 (1 × 10\^9 CFU) Weeks 5, 8, 11, 14, 17 and 20 (up to 6 cycles every 21 days): pemetrexed (500 mg/m\^2) and cisplatin (75 mg/m\^2) Weeks 23 and 26: cyclophosphamide one day before CRS-207 Maintenance Vaccinations: cyclophosphamide one day before CRS-207 every 8 weeks (starting at Week 34) until disease progression Immunotherapy with cyclophosphamide plus chemotherapy: live attenuated double deleted Lm
Overall Study Progressive disease	4	4
Overall Study Adverse Event	1	2
Overall Study Withdrawal by Subject	2	0
Overall Study Death	1	0
Overall Study Clinical progression	3	2

Baseline Characteristics

Safety and Efficacy of Listeria in Combination With Chemotherapy as Front-line Treatment for Malignant Pleural Mesothelioma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Immunotherapy Plus Chemotherapy n=38 Participants Weeks 1 and 3: CRS-207 (1 × 10\^9 CFU) Weeks 5, 8, 11, 14, 17 and 20 (up to 6 cycles every 21 days): pemetrexed (500 mg/m\^2) and cisplatin (75 mg/m\^2) Weeks 23 and 26: CRS-207 Maintenance Vaccinations: CRS-207 every 8 weeks (starting at Week 34) until disease progression Immunotherapy plus chemotherapy: live attenuated double deleted Lm	Immunotherapy With Cyclophosphamide Plus Chemotherapy n=22 Participants Weeks 1 and 3: cyclophosphamide (200 mg/m\^2), CRS-207 (1 × 10\^9 CFU) Weeks 5, 8, 11, 14, 17 and 20 (up to 6 cycles every 21 days): pemetrexed (500 mg/m\^2) and cisplatin (75 mg/m\^2) Weeks 23 and 26: cyclophosphamide one day before CRS-207 Maintenance Vaccinations: cyclophosphamide one day before CRS-207 every 8 weeks (starting at Week 34) until disease progression Immunotherapy with cyclophosphamide plus chemotherapy: live attenuated double deleted Lm	Total n=60 Participants Total of all reporting groups
Age, Customized <65 years	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Age, Customized >=65 years	29 Participants n=5 Participants	16 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	17 Participants n=7 Participants	51 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	37 Participants n=5 Participants	22 Participants n=7 Participants	59 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	36 Participants n=5 Participants	22 Participants n=7 Participants	58 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Weight	81.63 kg STANDARD_DEVIATION 16.203 • n=5 Participants	73.83 kg STANDARD_DEVIATION 12.340 • n=7 Participants	78.77 kg STANDARD_DEVIATION 15.271 • n=5 Participants
Height	174.51 cm STANDARD_DEVIATION 8.295 • n=5 Participants	168.41 cm STANDARD_DEVIATION 7.102 • n=7 Participants	172.28 cm STANDARD_DEVIATION 8.359 • n=5 Participants
Body Mass Index	26.702 kg/m^2 STANDARD_DEVIATION 4.3292 • n=5 Participants	26.076 kg/m^2 STANDARD_DEVIATION 4.4584 • n=7 Participants	26.473 kg/m^2 STANDARD_DEVIATION 4.3498 • n=5 Participants
Body Surface Area	1.982 m^2 STANDARD_DEVIATION 0.2230 • n=5 Participants	1.852 m^2 STANDARD_DEVIATION 0.1756 • n=7 Participants	1.935 m^2 STANDARD_DEVIATION 0.2148 • n=5 Participants

PRIMARY outcome

Timeframe: From first study dose until 28 days after the final dose (an average of 44 weeks)

Population: Safety Analysis Set (all participants who received \>= 1 dose of study treatment)

Count of subjects with incidences of adverse events.

Outcome measures

Outcome measures
Measure	Immunotherapy Plus Chemotherapy n=38 Participants Weeks 1 and 3: CRS-207 (1 × 10\^9 CFU) Weeks 5, 8, 11, 14, 17 and 20 (up to 6 cycles every 21 days): pemetrexed (500 mg/m\^2) and cisplatin (75 mg/m\^2) Weeks 23 and 26: CRS-207 Maintenance Vaccinations: CRS-207 every 8 weeks (starting at Week 34) until disease progression Immunotherapy plus chemotherapy: live attenuated double deleted Lm	Immunotherapy With Cyclophosphamide Plus Chemotherapy n=22 Participants Weeks 1 and 3: cyclophosphamide (200 mg/m\^2), CRS-207 (1 × 10\^9 CFU) Weeks 5, 8, 11, 14, 17 and 20 (up to 6 cycles every 21 days): pemetrexed (500 mg/m\^2) and cisplatin (75 mg/m\^2) Weeks 23 and 26: cyclophosphamide one day before CRS-207 Maintenance Vaccinations: cyclophosphamide one day before CRS-207 every 8 weeks (starting at Week 34) until disease progression Immunotherapy with cyclophosphamide plus chemotherapy: live attenuated double deleted Lm
Number of Subjects Reporting Adverse Events	38 Participants	22 Participants

PRIMARY outcome

Timeframe: Change over time assessed at multiple time points until disease progression or death (up to 12 months or longer)

Population: Immune response to mesothelin was not assessed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to measured disease progression or death (up to 12 months or longer)

Population: Safety analysis set: all enrolled subjects who received at least one dose of study treatment and had measurable disease.

Objective tumor response was measured using modified Response Evaluation Criteria in Solid Tumors (mRECIST) for assessment of response in malignant pleural mesothelioma (MPM). Per mRECIST for target lesions and assessed by CT: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease, those who fulfilled the criteria for neither PR nor PD; Progressive Disease (PD), \>=20% increase in the sum of the longest diameter of target lesions.

Outcome measures

Outcome measures
Measure	Immunotherapy Plus Chemotherapy n=36 Participants Weeks 1 and 3: CRS-207 (1 × 10\^9 CFU) Weeks 5, 8, 11, 14, 17 and 20 (up to 6 cycles every 21 days): pemetrexed (500 mg/m\^2) and cisplatin (75 mg/m\^2) Weeks 23 and 26: CRS-207 Maintenance Vaccinations: CRS-207 every 8 weeks (starting at Week 34) until disease progression Immunotherapy plus chemotherapy: live attenuated double deleted Lm	Immunotherapy With Cyclophosphamide Plus Chemotherapy n=21 Participants Weeks 1 and 3: cyclophosphamide (200 mg/m\^2), CRS-207 (1 × 10\^9 CFU) Weeks 5, 8, 11, 14, 17 and 20 (up to 6 cycles every 21 days): pemetrexed (500 mg/m\^2) and cisplatin (75 mg/m\^2) Weeks 23 and 26: cyclophosphamide one day before CRS-207 Maintenance Vaccinations: cyclophosphamide one day before CRS-207 every 8 weeks (starting at Week 34) until disease progression Immunotherapy with cyclophosphamide plus chemotherapy: live attenuated double deleted Lm
Objective Tumor Response Complete Response	1 Participants	0 Participants
Objective Tumor Response Partial Response	19 Participants	11 Participants
Objective Tumor Response Stable Disease	14 Participants	8 Participants
Objective Tumor Response Progressive Disease	1 Participants	2 Participants
Objective Tumor Response Not Assessable	1 Participants	0 Participants

SECONDARY outcome

Timeframe: From date of randomization until date of documented progression (by modified RECIST or immune-related response criteria) or death, assessed up to 12 months or longer

Population: Time to progression was not assessed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Change over time assessed at multiple time points until disease progression or death (up to 12 months or longer)

Population: Predictive value of serum mesothelin was not assessed.

Outcome measures

Outcome data not reported

Adverse Events

Immunotherapy Plus Chemotherapy

Serious events: 15 serious events

Other events: 38 other events

Deaths: 3 deaths

Immunotherapy With Cyclophosphamide Plus Chemotherapy

Serious events: 11 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Corporate Communications

Aduro Biotech, Inc.

Phone: 510-848-4400

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Disclosure restriction - study results first published in a joint multi-center paper unless (a) no multi-center publication, or (b) ≥18 months has passed since completion of the study. Thereafter, Investigator may publish provided that Investigator: (i) provides a copy of the publication to Aduro ≥ 30 days in advance of submission for publication; (ii) deletes Aduro Confidential Information (other than the Study results) and (iii) submission may be delayed up to 90 days to permit IP filings."
Publication restrictions are in place

Restriction type: OTHER

Measure	Immunotherapy Plus Chemotherapy n=38 participants at risk Weeks 1 and 3: CRS-207 (1 × 10\^9 CFU) Weeks 5, 8, 11, 14, 17 and 20 (up to 6 cycles every 21 days): pemetrexed (500 mg/m\^2) and cisplatin (75 mg/m\^2) Weeks 23 and 26: CRS-207 Maintenance Vaccinations: CRS-207 every 8 weeks (starting at Week 34) until disease progression Immunotherapy plus chemotherapy: live attenuated double deleted Lm	Immunotherapy With Cyclophosphamide Plus Chemotherapy n=22 participants at risk Weeks 1 and 3: cyclophosphamide (200 mg/m\^2), CRS-207 (1 × 10\^9 CFU) Weeks 5, 8, 11, 14, 17 and 20 (up to 6 cycles every 21 days): pemetrexed (500 mg/m\^2) and cisplatin (75 mg/m\^2) Weeks 23 and 26: cyclophosphamide one day before CRS-207 Maintenance Vaccinations: cyclophosphamide one day before CRS-207 every 8 weeks (starting at Week 34) until disease progression Immunotherapy with cyclophosphamide plus chemotherapy: live attenuated double deleted Lm
Gastrointestinal disorders Constipation	5.3% 2/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	4.5% 1/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Gastrointestinal disorders Nausea	5.3% 2/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	0.00% 0/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Gastrointestinal disorders Vomiting	5.3% 2/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	0.00% 0/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Gastrointestinal disorders Abdominal pain	0.00% 0/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	4.5% 1/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Gastrointestinal disorders Diarrhoea	2.6% 1/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	0.00% 0/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Gastrointestinal disorders Diverticular perforation	0.00% 0/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	4.5% 1/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Gastrointestinal disorders Gastric ulcer haemorrhage	2.6% 1/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	0.00% 0/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Gastrointestinal disorders Large intestine perforation	0.00% 0/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	4.5% 1/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Gastrointestinal disorders Pancreatitis acute	2.6% 1/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	0.00% 0/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Gastrointestinal disorders Small intestinal obstruction	2.6% 1/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	0.00% 0/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Respiratory, thoracic and mediastinal disorders Dyspnoea	7.9% 3/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	0.00% 0/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Respiratory, thoracic and mediastinal disorders Haemothorax	2.6% 1/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	0.00% 0/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	4.5% 1/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	4.5% 1/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.6% 1/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	0.00% 0/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
General disorders Chills	2.6% 1/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	4.5% 1/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
General disorders Pyrexia	2.6% 1/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	4.5% 1/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
General disorders Disease progression	2.6% 1/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	0.00% 0/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
General disorders Influenza like illness	0.00% 0/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	4.5% 1/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Infections and infestations Pneumonia	2.6% 1/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	9.1% 2/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Infections and infestations Sepsis	0.00% 0/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	4.5% 1/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Blood and lymphatic system disorders Anaemia	2.6% 1/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	4.5% 1/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Nervous system disorders Headache	2.6% 1/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	0.00% 0/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Nervous system disorders Syncope	0.00% 0/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	4.5% 1/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Cardiac disorders Atrial fibrillation	2.6% 1/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	0.00% 0/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Metabolism and nutrition disorders Hypoglycaemia	2.6% 1/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	0.00% 0/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Musculoskeletal and connective tissue disorders Polyarthritis	2.6% 1/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	0.00% 0/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Spinal cord neoplasm	2.6% 1/38 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.	0.00% 0/22 • From the start of the first study drug administration until 28 days after the last study drug dose, assessed up to 5 years from the date of randomization.