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

• Sponsor: Aduro Biotech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01675765
• Collaborator: (none)
• Enrollment: 60
• Locations: 5
• Arms: 2
• Actual Duration (Months): 59.5
• Patients Per Site: 12
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This clinical trial will evaluate the safety and immune response of the sequential administration cancer vaccine CRS-207 (with or without cyclophosphamide) followed by standard of care chemotherapy (pemetrexed and cisplatin). CRS-207 is a weakened (attenuated) form of Listeria monocytogenes that has been genetically-modified to reduce its capacity to cause disease, while maintaining its ability to stimulate potent immune responses. CRS-207 has been engineered to elicit an immune response against the tumor-associated antigen mesothelin, which has been shown to be present at higher levels on certain tumor cells (such as mesothelioma) than on normal cells. Pemetrexed and cisplatin are the standard chemotherapy regimen to treat malignant pleural mesothelioma. This trial will evaluate whether giving CRS-207 cancer vaccine with chemotherapy will induce anti-tumor immune responses and/or objective tumor response.

Condition or Disease	Intervention/Treatment	Phase
Malignant Pleural Mesothelioma	Biological: Immunotherapy plus chemotherapy; Biological: Immunotherapy with cyclophosphamide plus chemotherapy	Phase 1

Detailed Description

Up to 60 subjects will be enrolled in this study. Eligible subjects will receive 2 prime vaccinations of CRS-207 (1×10^9 colony-forming units [CFU] given intravenously [i.v.] over 2 hours) (with or without cyclophosphamide) 2 weeks apart followed 2 weeks later by up to 6 cycles of pemetrexed and cisplatin 21 days apart. Three weeks after completion of chemotherapy, subjects will receive an additional 2 infusions (boost vaccinations) of CRS-207 3 weeks apart. Subjects will be followed every 8 weeks until disease progression by immune-related response criteria. Subjects who continue to meet dosing eligibility may receive additional CRS-207 (with or without cyclophosphamide) infusions (maintenance vaccinations) at each follow-up visit.

Study assessments include blood draws for safety and immune response monitoring and CT scans [with optional fluorodeoxyglucose positron emission tomography (FDG-PET)] or magnetic resonance imaging (MRI) to monitor disease status. In addition, optional tumor biopsies may be performed before, during and after treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1B Study to Evaluate the Safety and Induction of Immune Response of CRS-207 in Combination With Pemetrexed and Cisplatin as Front-line Therapy in Adults With Malignant Pleural Mesothelioma
• Actual Study Start Date: Sep 3, 2014
• Actual Primary Completion Date: Sep 5, 2018
• Actual Study Completion Date: Aug 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Biological: Immunotherapy plus chemotherapy; live attenuated double deleted Lm; Other Names: CRS-207 Listeria pemetrexed cisplatin ALIMTA Platinol
Experimental: 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	Biological: Immunotherapy with cyclophosphamide plus chemotherapy; live attenuated double deleted Lm; Other Names: CRS-207 Cytoxan pemetrexed cisplatin ALIMTA Platinol Listeria

Outcome Measures

Primary Outcome Measures

1. Number of Subjects Reporting Adverse Events [From first study dose until 28 days after the final dose (an average of 44 weeks)]

   Count of subjects with incidences of adverse events.

2. Induction of Immune Response to Mesothelin by Enzyme-linked Immunosorbent Spot (ELISPOT) Assay [Change over time assessed at multiple time points until disease progression or death (up to 12 months or longer)]

Secondary Outcome Measures

1. Objective Tumor Response [Baseline to measured disease progression or death (up to 12 months or longer)]

   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.

2. Time to Progression [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]

3. Serum Mesothelin as Correlate of Therapeutic Response [Change over time assessed at multiple time points until disease progression or death (up to 12 months or longer)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Have histologically confirmed epithelial or biphasic MPM not amenable to potentially curative surgical resection (subjects with biphasic tumors that have a predominantly (≥50%) sarcomatoid component will be excluded)

• Be at least 18 years of age

• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Have an anticipated life expectancy of greater than 6 months

• For women and men of childbearing potential, a medically acceptable method of highly effective contraception (oral hormonal contraceptive, condom plus spermicide, or hormone implants) must be used throughout the study period and for 28 days after their final vaccine administration. (A barrier method of contraception must be employed by all subjects [male and female], regardless of other methods.)

• Be willing and able to give written informed consent, and be able to comply with all study procedures

• Have adequate organ function as defined by specified laboratory values

Exclusion Criteria:

• A candidate for curative surgery

• Surgery within 2 weeks prior to dosing

• Prior radiotherapy or biologic therapy

• Treatment with an investigational agent within 4 weeks before dosing

• Prior systemic chemotherapy

• Currently have or have history of certain study-specified heart, liver, kidney, lung, neurological, immune or other medical conditions

• Documented and ongoing brain metastases

• Have any evidence of hepatic cirrhosis or clinical or radiographic ascites

• Have clinically significant and/or malignant pleural effusion

• Known or suspected allergy or hypersensitivity to yeast or any other component of CRS-207 (e.g., glycerol), Platinol or platinum-containing compounds, or pemetrexed

• Used any systemic steroids within 28 days of study treatment

• Use more than 3 g/d of acetaminophen

• An artificial (prosthetic) joint or other artificial implant or device that cannot be easily removed (with some exceptions for dental and breast implants and biliary stents and mediports)

• Infection with HIV or hepatitis B or C at screening

• Any immunodeficiency disease or immunocompromised state or active autoimmune disease or history of autoimmune disease requiring systemic steroids or other immunosuppressive treatment

• Be a woman who is pregnant or breastfeeding

• Unable to avoid close contact with another individual known to be at high risk of listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the course of CRS-207 treatment until completion of antibiotic regimen

• Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California at San Francisco	San Francisco	California	United States	94115
2	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33612
3	University of Chicago Medical Center	Chicago	Illinois	United States	60637
4	National Cancer Institute	Bethesda	Maryland	United States	20892
5	University of Pennsylvania Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Aduro Biotech, Inc.

Investigators

• Principal Investigator: Raffit Hassan, MD, National Cancer Institute (NCI)

Study Documents (Full-Text)

• Study Protocol - Mar 8, 2018
• Statistical Analysis Plan - May 4, 2018

More Information

Publications

• Le DT, Dubenksy TW Jr, Brockstedt DG. Clinical development of Listeria monocytogenes-based immunotherapies. Semin Oncol. 2012 Jun;39(3):311-22. doi: 10.1053/j.seminoncol.2012.02.008. Review.

• Responsible Party: Aduro Biotech, Inc.
• ClinicalTrials.gov Identifier: NCT01675765
• Other Study ID Numbers: ADU-CL-02
• First Posted: Aug 30, 2012
• Last Update Posted: Sep 30, 2020
• Last Verified: Sep 1, 2020

• Keywords provided by Aduro Biotech, Inc.: Cancer; Cancer vaccine; Listeria monocytogenes; Listeria-based vaccines; Pemetrexed; Cisplatin; T regulatory cells; Mesothelin; Malignant Pleural Mesothelioma; Chemotherapy; Standard of care; Naive; Front-line; Immunotherapy; MPM
• Additional relevant MeSH terms: Mesothelioma; Mesothelioma, Malignant; Cyclophosphamide; Cisplatin; Pemetrexed; Immunologic Factors

Study Results

Participant Flow

Arm/Group Title	Immunotherapy Plus Chemotherapy	Immunotherapy With Cyclophosphamide Plus Chemotherapy
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	38	22
COMPLETED	27	14
NOT COMPLETED	11	8

Baseline Characteristics

Arm/Group Title	Immunotherapy Plus Chemotherapy	Immunotherapy With Cyclophosphamide Plus Chemotherapy	Total
Arm/Group Description	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	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 of all reporting groups
Overall Participants	38	22	60
Age, Customized (Count of Participants)
<65 years	9 23.7%	6 27.3%	15 25%
>=65 years	29 76.3%	16 72.7%	45 75%
Sex: Female, Male (Count of Participants)
Female	4 10.5%	5 22.7%	9 15%
Male	34 89.5%	17 77.3%	51 85%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 2.6%	0 0%	1 1.7%
Not Hispanic or Latino	37 97.4%	22 100%	59 98.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 5.3%	0 0%	2 3.3%
White	36 94.7%	22 100%	58 96.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	81.63 (16.203)	73.83 (12.340)	78.77 (15.271)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	174.51 (8.295)	168.41 (7.102)	172.28 (8.359)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.702 (4.3292)	26.076 (4.4584)	26.473 (4.3498)
Body Surface Area (m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [m^2]	1.982 (0.2230)	1.852 (0.1756)	1.935 (0.2148)

Outcome Measures

1. Primary Outcome

Title	Number of Subjects Reporting Adverse Events
Description	Count of subjects with incidences of adverse events.
Time Frame	From first study dose until 28 days after the final dose (an average of 44 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Immunotherapy Plus Chemotherapy	Immunotherapy With Cyclophosphamide Plus Chemotherapy
Arm/Group Description	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	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
Measure Participants	38	22
Count of Participants [Participants]	38 100%	22 100%

2. Primary Outcome

Title	Induction of Immune Response to Mesothelin by Enzyme-linked Immunosorbent Spot (ELISPOT) Assay
Time Frame	Change over time assessed at multiple time points until disease progression or death (up to 12 months or longer)

Outcome Measure Data

Analysis Population Description

Immune response to mesothelin was not assessed.

Arm/Group Title	Immunotherapy Plus Chemotherapy	Immunotherapy With Cyclophosphamide Plus Chemotherapy
Arm/Group Description	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	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
Measure Participants	0	0

3. Secondary Outcome

Title	Objective Tumor Response
Description	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.
Time Frame	Baseline to measured disease progression or death (up to 12 months or longer)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Immunotherapy Plus Chemotherapy	Immunotherapy With Cyclophosphamide Plus Chemotherapy
Arm/Group Description	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	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
Measure Participants	36	21
Complete Response	1 2.6%	0 0%
Partial Response	19 50%	11 50%
Stable Disease	14 36.8%	8 36.4%
Progressive Disease	1 2.6%	2 9.1%
Not Assessable	1 2.6%	0 0%

4. Secondary Outcome

Title	Time to Progression
Time Frame	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

Outcome Measure Data

Analysis Population Description

Time to progression was not assessed.

Arm/Group Title	Immunotherapy Plus Chemotherapy	Immunotherapy With Cyclophosphamide Plus Chemotherapy
Arm/Group Description	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	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
Measure Participants	0	0

5. Secondary Outcome

Title	Serum Mesothelin as Correlate of Therapeutic Response
Time Frame	Change over time assessed at multiple time points until disease progression or death (up to 12 months or longer)

Outcome Measure Data

Analysis Population Description

Predictive value of serum mesothelin was not assessed.

Arm/Group Title	Immunotherapy Plus Chemotherapy	Immunotherapy With Cyclophosphamide Plus Chemotherapy
Arm/Group Description	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	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
Measure Participants	0	0

Adverse Events

Time Frame	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.
Arm/Group Title	Immunotherapy Plus Chemotherapy		Immunotherapy With Cyclophosphamide Plus Chemotherapy
Arm/Group Description	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		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
All Cause Mortality
	Immunotherapy Plus Chemotherapy		Immunotherapy With Cyclophosphamide Plus Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/38 (7.9%)		0/22 (0%)
Serious Adverse Events
	Immunotherapy Plus Chemotherapy		Immunotherapy With Cyclophosphamide Plus Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/38 (39.5%)		11/22 (50%)
Blood and lymphatic system disorders
Anaemia	1/38 (2.6%)		1/22 (4.5%)
Cardiac disorders
Atrial fibrillation	1/38 (2.6%)		0/22 (0%)
Gastrointestinal disorders
Constipation	2/38 (5.3%)		1/22 (4.5%)
Nausea	2/38 (5.3%)		0/22 (0%)
Vomiting	2/38 (5.3%)		0/22 (0%)
Abdominal pain	0/38 (0%)		1/22 (4.5%)
Diarrhoea	1/38 (2.6%)		0/22 (0%)
Diverticular perforation	0/38 (0%)		1/22 (4.5%)
Gastric ulcer haemorrhage	1/38 (2.6%)		0/22 (0%)
Large intestine perforation	0/38 (0%)		1/22 (4.5%)
Pancreatitis acute	1/38 (2.6%)		0/22 (0%)
Small intestinal obstruction	1/38 (2.6%)		0/22 (0%)
General disorders
Chills	1/38 (2.6%)		1/22 (4.5%)
Pyrexia	1/38 (2.6%)		1/22 (4.5%)
Disease progression	1/38 (2.6%)		0/22 (0%)
Influenza like illness	0/38 (0%)		1/22 (4.5%)
Infections and infestations
Pneumonia	1/38 (2.6%)		2/22 (9.1%)
Sepsis	0/38 (0%)		1/22 (4.5%)
Metabolism and nutrition disorders
Hypoglycaemia	1/38 (2.6%)		0/22 (0%)
Musculoskeletal and connective tissue disorders
Polyarthritis	1/38 (2.6%)		0/22 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Spinal cord neoplasm	1/38 (2.6%)		0/22 (0%)
Nervous system disorders
Headache	1/38 (2.6%)		0/22 (0%)
Syncope	0/38 (0%)		1/22 (4.5%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	3/38 (7.9%)		0/22 (0%)
Haemothorax	1/38 (2.6%)		0/22 (0%)
Hypoxia	0/38 (0%)		1/22 (4.5%)
Pleuritic pain	0/38 (0%)		1/22 (4.5%)
Pulmonary embolism	1/38 (2.6%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Immunotherapy Plus Chemotherapy		Immunotherapy With Cyclophosphamide Plus Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/38 (100%)		22/22 (100%)
Blood and lymphatic system disorders
Anaemia	15/38 (39.5%)		8/22 (36.4%)
Neutropenia	3/38 (7.9%)		3/22 (13.6%)
Leukopenia	3/38 (7.9%)		0/22 (0%)
Leukocytosis	2/38 (5.3%)		0/22 (0%)
Cardiac disorders
Sinus tachycardia	4/38 (10.5%)		1/22 (4.5%)
Atrial fibrillation	1/38 (2.6%)		2/22 (9.1%)
Tachycardia	2/38 (5.3%)		1/22 (4.5%)
Ear and labyrinth disorders
Tinnitus	5/38 (13.2%)		1/22 (4.5%)
Vertigo	2/38 (5.3%)		0/22 (0%)
Eye disorders
Lacrimation increased	6/38 (15.8%)		1/22 (4.5%)
Gastrointestinal disorders
Nausea	31/38 (81.6%)		12/22 (54.5%)
Vomiting	25/38 (65.8%)		5/22 (22.7%)
Constipation	15/38 (39.5%)		7/22 (31.8%)
Diarrhoea	8/38 (21.1%)		2/22 (9.1%)
Abdominal pain	4/38 (10.5%)		5/22 (22.7%)
Dry mouth	4/38 (10.5%)		0/22 (0%)
Ascites	2/38 (5.3%)		1/22 (4.5%)
Gastrooesophageal reflux disease	2/38 (5.3%)		1/22 (4.5%)
Abdominal discomfort	2/38 (5.3%)		0/22 (0%)
Dyspepsia	2/38 (5.3%)		0/22 (0%)
Flatulence	0/38 (0%)		2/22 (9.1%)
General disorders
Chills	37/38 (97.4%)		22/22 (100%)
Pyrexia	37/38 (97.4%)		21/22 (95.5%)
Fatigue	23/38 (60.5%)		12/22 (54.5%)
Oedema peripheral	7/38 (18.4%)		3/22 (13.6%)
Non-cardiac chest pain	5/38 (13.2%)		0/22 (0%)
Malaise	3/38 (7.9%)		0/22 (0%)
Chest pain	2/38 (5.3%)		0/22 (0%)
Oedema	2/38 (5.3%)		0/22 (0%)
Mucosal inflammation	2/38 (5.3%)		0/22 (0%)
Infections and infestations
Upper respiratory tract infection	3/38 (7.9%)		1/22 (4.5%)
Pneumonia	1/38 (2.6%)		2/22 (9.1%)
Sinusitis	2/38 (5.3%)		1/22 (4.5%)
Urinary tract infection	3/38 (7.9%)		0/22 (0%)
Investigations
Blood creatinine increased	6/38 (15.8%)		7/22 (31.8%)
White blood cell count decreased	7/38 (18.4%)		3/22 (13.6%)
Alanine aminotransferase increased	7/38 (18.4%)		1/22 (4.5%)
Lymphocyte count decreased	5/38 (13.2%)		3/22 (13.6%)
Neutrophil count decreased	7/38 (18.4%)		1/22 (4.5%)
Aspartate aminotransferase increased	6/38 (15.8%)		1/22 (4.5%)
Platelet count decreased	5/38 (13.2%)		2/22 (9.1%)
Weight decreased	4/38 (10.5%)		2/22 (9.1%)
Blood alkaline phosphatase increased	1/38 (2.6%)		3/22 (13.6%)
Haemoglobin decreased	2/38 (5.3%)		2/22 (9.1%)
Blood urea increased	3/38 (7.9%)		0/22 (0%)
Weight increased	3/38 (7.9%)		0/22 (0%)
Blood albumin decreased	2/38 (5.3%)		0/22 (0%)
Haematocrit decreased	0/38 (0%)		2/22 (9.1%)
Metabolism and nutrition disorders
Decreased appetite	19/38 (50%)		4/22 (18.2%)
Hyponatraemia	8/38 (21.1%)		3/22 (13.6%)
Hypoalbuminaemia	7/38 (18.4%)		3/22 (13.6%)
Hypomagnesaemia	6/38 (15.8%)		4/22 (18.2%)
Hyperglycaemia	7/38 (18.4%)		2/22 (9.1%)
Hyperkalaemia	5/38 (13.2%)		4/22 (18.2%)
Dehydration	5/38 (13.2%)		2/22 (9.1%)
Hypophosphataemia	5/38 (13.2%)		1/22 (4.5%)
Hypocalcaemia	4/38 (10.5%)		1/22 (4.5%)
Musculoskeletal and connective tissue disorders
Back pain	7/38 (18.4%)		3/22 (13.6%)
Musculoskeletal chest pain	2/38 (5.3%)		2/22 (9.1%)
Musculoskeletal pain	3/38 (7.9%)		1/22 (4.5%)
Arthralgia	3/38 (7.9%)		0/22 (0%)
Muscular weakness	2/38 (5.3%)		0/22 (0%)
Myalgia	2/38 (5.3%)		0/22 (0%)
Pain in extremity	0/38 (0%)		2/22 (9.1%)
Nervous system disorders
Headache	11/38 (28.9%)		6/22 (27.3%)
Dizziness	8/38 (21.1%)		1/22 (4.5%)
Neuropathy peripheral	6/38 (15.8%)		2/22 (9.1%)
Dysgeusia	5/38 (13.2%)		0/22 (0%)
Syncope	2/38 (5.3%)		2/22 (9.1%)
Tremor	2/38 (5.3%)		0/22 (0%)
Psychiatric disorders
Insomnia	4/38 (10.5%)		5/22 (22.7%)
Anxiety	1/38 (2.6%)		2/22 (9.1%)
Depression	2/38 (5.3%)		1/22 (4.5%)
Renal and urinary disorders
Renal impairment	0/38 (0%)		2/22 (9.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	10/38 (26.3%)		5/22 (22.7%)
Cough	8/38 (21.1%)		0/22 (0%)
Rhinorrhoea	6/38 (15.8%)		2/22 (9.1%)
Hiccups	6/38 (15.8%)		1/22 (4.5%)
Hypoxia	1/38 (2.6%)		4/22 (18.2%)
Dyspnoea exertional	3/38 (7.9%)		1/22 (4.5%)
Pleural effusion	4/38 (10.5%)		0/22 (0%)
Dysphonia	3/38 (7.9%)		0/22 (0%)
Pulmonary embolism	3/38 (7.9%)		0/22 (0%)
Nasal congestion	0/38 (0%)		2/22 (9.1%)
Tachypnoea	2/38 (5.3%)		0/22 (0%)
Throat irritation	2/38 (5.3%)		0/22 (0%)
Skin and subcutaneous tissue disorders
Rash	6/38 (15.8%)		1/22 (4.5%)
Night sweats	5/38 (13.2%)		1/22 (4.5%)
Rash maculo-papular	4/38 (10.5%)		1/22 (4.5%)
Hyperhidrosis	4/38 (10.5%)		0/22 (0%)
Pruritus	4/38 (10.5%)		0/22 (0%)
Urticaria	3/38 (7.9%)		0/22 (0%)
Vascular disorders
Hypotension	9/38 (23.7%)		4/22 (18.2%)
Hypertension	6/38 (15.8%)		2/22 (9.1%)
Flushing	3/38 (7.9%)		1/22 (4.5%)
Deep vein thrombosis	2/38 (5.3%)		0/22 (0%)
Jugular vein thrombosis	2/38 (5.3%)		0/22 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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."