A Trial Comparing Gemcitabine With and Without IMM-101 in Advanced Pancreatic Cancer

• Sponsor: Immodulon Therapeutics Ltd (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01303172
• Collaborator: (none)
• Enrollment: 110
• Locations: 21
• Arms: 2
• Actual Duration (Months): 55
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To compare, in patients with advanced pancreatic cancer, the effects of IMM-101 in combination with gemcitabine to gemcitabine alone on safety and tolerability (including QoL), clinical signs and symptoms of disease, selected markers of tumour burden and immunological status, and disease outcome.

Condition or Disease	Intervention/Treatment	Phase
Advanced Pancreatic Cancer	Biological: IMM-101; Drug: Gemcitabine	Phase 2

Detailed Description

Patients in the IMM 101 treated group received an initial dose of IMM-101 followed by a maximum of 12 cycles of Gemcitabine (plus IMM-101); patients in the control group received Gemcitabine alone. All patients were to receive Gemcitabine once weekly for 3 consecutive weeks out of every 4 weeks. Patients in the IMM 101 treated group were to receive IMM 101 every 2 weeks for the first 3 doses, followed by a 4 week rest, then IMM-101 every 2 weeks for the next 3 doses. After this time, patients received doses every 4 weeks. Gemcitabine treatment began at least 14 days after the first dose of IMM-101 in the IMM 101 treated group.

Patients who completed the Main Study and who provided informed consent were eligible to participate in a long term treatment Sub-Study. All patients received IMM-101 in the open-label, single arm, Sub-Study irrespective of whether they had been randomised to Gemcitabine or Gemcitabine plus IMM-101 in the main study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 110 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomised, Open-Label, Proof-of-Concept, Phase II Trial Comparing Gemcitabine With and Without IMM-101 in Advanced Pancreatic Cancer
• Actual Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Jun 1, 2014
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Gemcitabine chemotherapy Patients in the control arm will receive normal standard of care - up to 12 cycles of Gemcitabine. Dosing of Gemcitabine is as per the normal prescribing information for pancreatic cancer.	Drug: Gemcitabine; Gemcitabine will be administered intravenously at 1000 mg/m2 over 30 minutes once weekly for 3 consecutive weeks out of every 4 weeks. Chemotherapy will be offered until intolerable toxicity or withdrawal from the study up to a maximum of 12 cycles (i.e. approximately 48 weeks). Dosage reduction with each cycle or within each cycle may be applied based upon the grade of Gemcitabine-related toxicity experienced by the patient using centre's standard protocol.; Other Names: Gemzar
Experimental: IMM-101 in addition to gemcitabine Patients in the experimental arm will receive IMM-101 in addition to the current standard of care, namely chemotherapy (Gemcitabine). The treatment regimen with IMM-101 will be every 2 weeks for the first 3 doses followed by a rest of 4 weeks then every 2 weeks for the next 3 doses followed by every 4 weeks thereafter. For patients in the active group, chemotherapy (Gemcitabine) will begin at least 14 days after first dose of IMM-101. Chemotherapy plus IMM-101 will be offered until intolerable toxicity or withdrawal from the study up to a maximum of 12 cycles (i.e. approximately 48 weeks). Patients who complete the Main Study and who provide informed consent are eligible to participate in a long term treatment Sub-Study (IMM-101-002A)	Biological: IMM-101; IMM-101 is a suspension of heat-killed whole cell M. obuense in borate-buffered saline. A single 0.1 mL intradermal injection of IMM-101 (10 mg/mL) will be administered every 2 weeks for the first 3 doses followed by a rest of 4 weeks then every 2 weeks for the next 3 doses followed by every 4 weeks thereafter. Chemotherapy plus IMM-101 will be offered until intolerable toxicity or withdrawal from the study up to a maximum of 12 cycles of gemcitabine.; Other Names: Heat killed whole cell Mycobacterium obuense (M. obuense)

Outcome Measures

Primary Outcome Measures

1. Safety and Tolerability. [From time of Informed Consent to 30 days post last dose of study medication]

   A clinically relevant deleterious effect of IMM-101 on safety and tolerability profiles was judged by: Local and systemic toxicities. Number, type and degree of toxicities as measured by the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) v4.0. Adverse events were collected from time of Informed Consent to 30 days post last dose of study medication IMM-101 does not appear to confer an incremental safety burden beyond that associated with chemotherapy and the disease itself. No new safety signals were identified from this study. The numbers of SAEs by preferred term were low, such that no trends could be inferred from these data and no significant SAEs attributable to IMM 101 were observed.

Secondary Outcome Measures

1. Survival [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year (or longer in the case of patients who entered the long term treatment sub-study, up to 5 years).]

   Overall and progression free survival

2. Overall Response Rate (ORR). [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year (or longer in the case of patients who entered the long term treatment sub-study).]

   A clinically relevant improvement Overall Response Rate (ORR). Overall response rate was defined as the percentage of patients with a complete response or partial response as assessed by RECIST v1.1 criteria.

3. Overall Survival in Metastatic Patients Only [From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year (or longer in the case of patients who entered the long term treatment sub-study, up to 5 years).]

   Overall and progression free survival in metastatic patients only

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female; aged ≥18 years.

• Histologically and/or cytologically confirmed inoperable ductal adenocarcinoma of the pancreas, including the mucinous variant. This will include locally advanced and metastatic disease (stage III/IV).

• Presence of measurable lesions in at least one site which have not been previously irradiated (bone lesions, ascites and pleural effusions are not considered as measurable), described as any of the following:

• Any primary tumour with at least bi-dimensionally measurable disease.

• 1. Palpable lymph nodes; b) Deep seated lymph nodes.

• Liver metastases measurable by computerised tomography (CT) scan.

• Deep seated soft tissue lesions measurable by CT scan.

• World Health Organization (WHO) performance status of 0-2

• Serum creatinine <140 μmol/L

• White blood cell (WBC) count, including differential counts within the normal range or, if outside the normal range, considered by the Investigator not to be clinically significant.

• Life expectancy of >3 months from randomisation.

• Provided written informed consent to participate as shown by a signature and date on the patient's Informed Consent Form

Exclusion Criteria:

• Acinar cell carcinoma, neuroendocrine tumours, lymphomas or squamous cell carcinomas.

• Severe, active uncontrolled infection requiring systemic antibiotics, antiviral or antifungal treatments.

• Any previous chemotherapy treatment for pancreatic cancer.

• Eligible for resection of the pancreatic primary tumour but has either refused the operation or is considered to be medically unfit for the operation.

• Clinical or CT evidence of central nervous system (CNS) metastases.

• Any previous or concurrent malignancy, except adequately treated carcinoma in situ of the cervix, basal cell carcinoma of the skin and/or non-melanoma skin cancer, or if previous malignancy was more than 5 years earlier and there were no signs of recurrence.

• Any previous treatment with IMM-101 or related mycobacterial immunotherapy.

• Serum albumin < 26 g/L.

• C-reactive protein (CRP) > 70 mg/L.

• Radiotherapy in the 6 weeks prior to screening.

• Depot corticosteroids in the 6 weeks prior to screening.

• Chronic use of any systemic corticosteroids and/or immunosuppressant drugs within the 2-week period prior to the first administration of study drug.

• Female patient of child-bearing potential who is not, in the opinion of the Investigator, using an approved method of birth control.

• Female patient who were pregnant, breast feeding or planning a pregnancy during the course of the study. A pre-treatment serum pregnancy test measuring human chorionic gonadotrophin (hCG) had to be negative.

• Had been administered any investigational product e.g. drug, vaccine or device, in the 3 months prior to screening.

• Surgical or medical condition which, in the judgement of the Investigator, might interfere with the activity of IMM-101, or with the performance of this study.

• Any uncontrolled concomitant disease (e.g. unstable angina pectoris, congestive heart failure, myocardial infarction, arrhythmias, and uncontrolled severe hypertension) which, in the judgement of the Investigator, might interfere with the activity of IMM 101, or with the performance of this study.

• A history of serious adverse reaction or serious hypersensitivity to any drug.

• Known to have a history of human immunodeficiency virus (HIV) or syphilis, current symptomatic Hepatitis B or C. Testing is not required in the absence of clinical signs and symptoms suggestive of infection with HIV.

• Unable or unwilling to comply with the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cyprus Oncology Centre	Nicosia	Strovolos	Cyprus	2006
2	Adelaide, Meath & National Childrens Hospital,	Dublin		Ireland	Dublin 24
3	St Vicents University Hospital	Dublin		Ireland	Dublin 4
4	Azienda Ospedaliero-Universitaria di Bologna	Bologna		Italy	40138
5	A.O. Santa Croce e Carle, Struttura Complessa di Oncologia Medica	Cuneo		Italy
6	Azienda Ospedaliera San Gerardo Struttura Complessa Oncologia Medica	Monza		Italy	20900
7	AOU Maggiore della Carità	Novara		Italy
8	Medical Oncology Department, Central University Hospital of Asturias	Oviedo	Asturias	Spain
9	Hospital General de Alicante	Alicante		Spain	03010
10	Hospital Gregorio Marañon	Madrid		Spain	28007
11	Instituto Valenciano de Oncologia	Valencia		Spain	46009
12	Department of Medical Oncology, Hospital Universitari La Fe,	Valencia		Spain	46026
13	Hospital Miguel Servet	Zaragoza		Spain	50009
14	Airedale General Hospital	Skipton	West Yorkshire	United Kingdom	BD20 6TD
15	Royal Blackburn Hospital	Blackburn		United Kingdom	BB2 3HH
16	Bradford Royal Infirmary	Bradford		United Kingdom	BD9 6RJ
17	Velindre Cancer Centre	Cardiff		United Kingdom	Velindre Cancer Centre
18	Ninewells Hospital,	Dundee		United Kingdom	DD1 9SY
19	Mount Vernon Cancer Centre	London		United Kingdom	HA6 2RN
20	The London Clinic Cancer Centre	London		United Kingdom	W1G 6BW
21	Peterbrough City Hospital, Haematology/Oncology Dept,	Peterborough		United Kingdom	PE3 9GZ

Sponsors and Collaborators

• Immodulon Therapeutics Ltd

Investigators

• Principal Investigator: Angus Dalgleish, Professor, St George's, University of London

Study Documents (Full-Text)

None provided.

More Information

Publications

• Dalgleish AG, Stebbing J, Adamson DJ, Arif SS, Bidoli P, Chang D, Cheeseman S, Diaz-Beveridge R, Fernandez-Martos C, Glynne-Jones R, Granetto C, Massuti B, McAdam K, McDermott R, Martín AJ, Papamichael D, Pazo-Cid R, Vieitez JM, Zaniboni A, Carroll KJ, Wagle S, Gaya A, Mudan SS. Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer. Br J Cancer. 2016 Sep 27;115(7):789-96. doi: 10.1038/bjc.2016.271. Epub 2016 Sep 6. Erratum in: Br J Cancer. 2016 Oct 25;115(9):e16.

• Responsible Party: Immodulon Therapeutics Ltd
• ClinicalTrials.gov Identifier: NCT01303172
• Other Study ID Numbers: IMM-101-002; IMAGE-1
• First Posted: Feb 24, 2011
• Last Update Posted: Nov 10, 2021
• Last Verified: Nov 1, 2021

• Additional relevant MeSH terms: Pancreatic Neoplasms; Gemcitabine

Study Results

Participant Flow

Arm/Group Title	Gemcitabine Plus IMM-101	Gemcitabine Monotherapy
Arm/Group Description	Patients in the experimental arm received IMM-101 in addition to Gemcitabine (Gem). The treatment regimen with IMM-101 was every 2 weeks for the first 3 doses followed by a rest of 4 weeks then every 2 weeks for the next 3 doses followed by every 4 weeks thereafter. For patients in the experimental group, GEM was initiated at least 14 days after first dose of IMM-101. GEM plus IMM-101 was offered until intolerable toxicity or withdrawal from the study up to a maximum of 12 cycles (i.e. approximately 48 weeks). IMM-101: IMM-101 is a suspension of heat-killed whole cell M. obuense in borate-buffered saline. A single 0.1 mL intradermal injection of IMM-101 (10 mg/mL)will be administered every 2 weeks for the first 3 doses followed by a rest of 4 weeks then every 2 weeks for the next 3 doses followed by every 4 weeks thereafter. Chemotherapy plus IMM-101 will be offered until intolerable toxicity or withdrawal from the study up to a maximum of 12 cycles of GEM. Patients who completed the Main Study and who provided informed consent were eligible to participate in a long term treatment Sub-Study where all patients received IMM-101.	Patients in the control arm received normal standard of care - up to 12 cycles of Gemcitabine. Dosing of Gemcitabine was as per the normal prescribing information for pancreatic cancer. Gemcitabine was administered intravenously at 1000 mg/m2 over 30 minutes once weekly for 3 consecutive weeks out of every 4 weeks until intolerable toxicity or withdrawal from the study up to a maximum of 12 cycles (i.e. approximately 48 weeks). Dosage reduction with each cycle or within each cycle was applied based upon the grade of Gemcitabine-related toxicity experienced by the patient using centre's standard protocol. Patients who completed the Main Study and who provided informed consent were eligible to participate in a long term treatment Sub-Study where all patients received IMM-101.
Period Title: Overall Study
STARTED	75	35
COMPLETED	12	1
NOT COMPLETED	63	34

Baseline Characteristics

Arm/Group Title	Experimental	Control	Total
Arm/Group Description	Gemcitabine plus IMM-101	Gemcitabine monotherapy	Total of all reporting groups
Overall Participants	75	35	110
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	28 37.3%	16 45.7%	44 40%
>=65 years	47 62.7%	19 54.3%	66 60%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	68	66	67
Sex: Female, Male (Count of Participants)
Female	37 49.3%	14 40%	51 46.4%
Male	38 50.7%	21 60%	59 53.6%
Race/Ethnicity, Customized (Count of Participants)
White	74 98.7%	33 94.3%	107 97.3%
Asian	1 1.3%	0 0%	1 0.9%
Other	0 0%	1 2.9%	1 0.9%
Unknown	0 0%	1 2.9%	1 0.9%
Region of Enrollment (participants) [Number]
Cyprus	3 4%	3 8.6%	6 5.5%
Ireland	1 1.3%	1 2.9%	2 1.8%
United Kingdom	25 33.3%	9 25.7%	34 30.9%
Italy	14 18.7%	9 25.7%	23 20.9%
Spain	32 42.7%	13 37.1%	45 40.9%

Outcome Measures

1. Primary Outcome

Title	Safety and Tolerability.
Description	A clinically relevant deleterious effect of IMM-101 on safety and tolerability profiles was judged by: Local and systemic toxicities. Number, type and degree of toxicities as measured by the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) v4.0. Adverse events were collected from time of Informed Consent to 30 days post last dose of study medication IMM-101 does not appear to confer an incremental safety burden beyond that associated with chemotherapy and the disease itself. No new safety signals were identified from this study. The numbers of SAEs by preferred term were low, such that no trends could be inferred from these data and no significant SAEs attributable to IMM 101 were observed.
Time Frame	From time of Informed Consent to 30 days post last dose of study medication

Outcome Measure Data

Analysis Population Description

The safety analysis set included all randomised patients who received at least one dose of the study drug. One patient in the Gemcitabine plus IMM-101 group was withdrawn prior to administration of study treatment due to a worsening of his physical condition.

Arm/Group Title	Experimental	Control
Arm/Group Description	Gemcitabine plus IMM-101	Gemcitabine monotherapy
Measure Participants	74	35
With Treatment Emergent Adverse Events (TEAEs)	73 97.3%	35 100%
Withdrawn due to a TEAE	4 5.3%	0 0%
With TEAEs related to IMM-101	43 57.3%	0 0%
With Treatment Emergent Serious Adverse Events (TESAEs)	38 50.7%	10 28.6%
With Treatment Emergent Serious Adverse Events (TESAEs) related to IMM-101	7 9.3%	0 0%

2. Secondary Outcome

Title	Survival
Description	Overall and progression free survival
Time Frame	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year (or longer in the case of patients who entered the long term treatment sub-study, up to 5 years).

Outcome Measure Data

Analysis Population Description

The Intent To Treat analysis set included all randomised patients.

Arm/Group Title	Experimental	Control
Arm/Group Description	Gemcitabine plus IMM-101	Gemcitabine monotherapy
Measure Participants	75	35
Overall Survival	6.7	5.6
Progression Free Survival	4.1	2.4

3. Secondary Outcome

Title	Overall Response Rate (ORR).
Description	A clinically relevant improvement Overall Response Rate (ORR). Overall response rate was defined as the percentage of patients with a complete response or partial response as assessed by RECIST v1.1 criteria.
Time Frame	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year (or longer in the case of patients who entered the long term treatment sub-study).

Outcome Measure Data

Analysis Population Description

The Intent To Treat analysis set included all randomised patients.

Arm/Group Title	Experimental	Control
Arm/Group Description	Gemcitabine plus IMM-101	Gemcitabine monotherapy
Measure Participants	75	35
Complete Response	0 0%	0 0%
Partial Response	8 10.7%	1 2.9%

4. Secondary Outcome

Title	Overall Survival in Metastatic Patients Only
Description	Overall and progression free survival in metastatic patients only
Time Frame	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year (or longer in the case of patients who entered the long term treatment sub-study, up to 5 years).

Outcome Measure Data

Analysis Population Description

The subgroup of patients with metastatic disease at baseline was the largest and accounted for 80.0% of patients in the ITT analysis set.

Arm/Group Title	Experimental	Control
Arm/Group Description	IMM-101 plus Gemcitabine	Gemcitabine monotherapy
Measure Participants	64	28
Median (95% Confidence Interval) [Months]	7.0	4.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Experimental, Control
	Comments	The difference between the two treatment groups was tested with a two-sided log-rank test and a Cox regression model was used to estimate the hazard ratio (HR) and its 95% CI and associated p-value.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Cox Proportional Hazard
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 95%; 0.33 to 0.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse event were collected and followed until resolution or for up to 30 days after the end of study/withdrawa
Adverse Event Reporting Description	It was the responsibility of the Investigator to document all AEs that occurred during the study. Adverse events were elicited by asking the patient a non-leading question, for example "Have you experienced or are you experiencing any new or changed symptoms since we last asked/since your last visit?" All AEs were followed until resolution or for up to 30 days after the end of study/withdrawal.
Arm/Group Title	Experimental		Control
Arm/Group Description	Gemcitabine plus IMM-101		Gemcitabine monotherapy
All Cause Mortality
	Experimental		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/75 (29.3%)		7/35 (20%)
Serious Adverse Events
	Experimental		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/75 (48%)		10/35 (28.6%)
Blood and lymphatic system disorders
Anaemia	2/75 (2.7%)	2	0/35 (0%)	0
Febrile neutropenia	1/75 (1.3%)	1	0/35 (0%)	0
Splenomegaly	1/75 (1.3%)	1	0/35 (0%)	0
Cardiac disorders
Arrhymia	1/75 (1.3%)	1	0/35 (0%)	0
Cardiac failure congestive	1/75 (1.3%)	1	0/35 (0%)	0
Gastrointestinal disorders
Abdominal pain	4/75 (5.3%)	4	0/35 (0%)	0
Ascites	3/75 (4%)	4	0/35 (0%)	0
Vomiting	3/75 (4%)	3	0/35 (0%)	0
Intestinal obstruction	1/75 (1.3%)	1	1/35 (2.9%)	1
Gastrointestinal hemorrhage	1/75 (1.3%)	1	0/35 (0%)	0
Diarrhea	0/75 (0%)	0	1/35 (2.9%)	1
Large intestine perforation	1/75 (1.3%)	1	0/35 (0%)	0
Pancreatic duct stenosis	1/75 (1.3%)	1	0/35 (0%)	0
Small intestine perforation	0/75 (0%)	0	1/35 (2.9%)	1
Upper gastrointestinal haemorrhage	1/75 (1.3%)	1	0/35 (0%)	0
General disorders
Disease progression	3/75 (4%)	3	2/35 (5.7%)	2
Pyrexia	4/75 (5.3%)	4	1/35 (2.9%)	1
Chest pain	1/75 (1.3%)	1	0/35 (0%)	0
Fatigue	1/75 (1.3%)	1	0/35 (0%)	0
General physical health deterioration	1/75 (1.3%)	1	0/35 (0%)	0
Mucosal inflammation	1/75 (1.3%)	1	0/35 (0%)	0
Sudden death	0/75 (0%)	0	1/35 (2.9%)	1
Hepatobiliary disorders
Bile duct obstruction	2/75 (2.7%)	2	0/35 (0%)	0
Cholangitis	1/75 (1.3%)	1	0/35 (0%)	0
Cholecystitis	1/75 (1.3%)	1	0/35 (0%)	0
Infections and infestations
Biliary sepsis	4/75 (5.3%)	6	0/35 (0%)	0
Infection	3/75 (4%)	3	0/35 (0%)	0
Pneumonia	3/75 (4%)	3	0/35 (0%)	0
Sepsis	1/75 (1.3%)	1	1/35 (2.9%)	2
Lower respiratory tract infection	2/75 (2.7%)	2	0/35 (0%)	0
Urinary tract infection	2/75 (2.7%)	2	0/35 (0%)	0
Biliary tract infection	1/75 (1.3%)	1	0/35 (0%)	0
Clostridium difficile colitis	1/75 (1.3%)	3	0/35 (0%)	0
Device related infection	1/75 (1.3%)	1	0/35 (0%)	0
Gastroenteritis	1/75 (1.3%)	1	0/35 (0%)	0
Liver abscess	1/75 (1.3%)	1	0/35 (0%)	0
Lung infection	1/75 (1.3%)	1	0/35 (0%)	0
Septic shock	0/75 (0%)	0	1/35 (2.9%)	1
Urinary tract infection fungal	1/75 (1.3%)	1	0/35 (0%)	0
Injury, poisoning and procedural complications
Incisional hernia	1/75 (1.3%)	1	0/35 (0%)	0
Toxicity to various agents	1/75 (1.3%)	1	0/35 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/75 (1.3%)	1	0/35 (0%)	0
Dehydration	0/75 (0%)	0	1/35 (2.9%)	1
Diabetic ketoacidosis	1/75 (1.3%)	1	0/35 (0%)	0
Hypoglycaemia	1/75 (1.3%)	1	0/35 (0%)	0
Hypokalaemia	0/75 (0%)	0	1/35 (2.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma metastatic	1/75 (1.3%)	1	0/35 (0%)	0
Nervous system disorders
Cerebral infarction	1/75 (1.3%)	1	1/35 (2.9%)	1
Cerebellar infarction	1/75 (1.3%)	1	0/35 (0%)	0
Convulsion	1/75 (1.3%)	1	0/35 (0%)	0
IVth nerve paralysis	0/75 (0%)	0	1/35 (2.9%)	1
Nerve root compression	1/75 (1.3%)	1	0/35 (0%)	0
Peroneal nerve palsy	1/75 (1.3%)	1	0/35 (0%)	0
Syncope	1/75 (1.3%)	1	0/35 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pleural effusion	2/75 (2.7%)	2	0/35 (0%)	0
Dyspnoea	1/75 (1.3%)	1	0/35 (0%)	0
Pneumonitis	1/75 (1.3%)	1	0/35 (0%)	0
Pneumothorax	1/75 (1.3%)	1	0/35 (0%)	0
Pulomonary embolism	1/75 (1.3%)	1	0/35 (0%)	0
Other (Not Including Serious) Adverse Events
	Experimental		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/75 (97.3%)		35/35 (100%)
Blood and lymphatic system disorders
Anaemia	23/75 (30.7%)	40	9/35 (25.7%)	14
Neutropenia	16/75 (21.3%)	48	10/35 (28.6%)	24
Thrombocytopenia	11/75 (14.7%)	21	7/35 (20%)	13
Leukopenia	4/75 (5.3%)	24	3/35 (8.6%)	9
Gastrointestinal disorders
Abdominal pain	35/75 (46.7%)	56	11/35 (31.4%)	22
Diarrhoea	33/75 (44%)	65	14/35 (40%)	27
Nausea	33/75 (44%)	59	13/35 (37.1%)	26
Constipation	31/75 (41.3%)	42	11/35 (31.4%)	21
Vomiting	22/75 (29.3%)	34	14/35 (40%)	19
Stomatitis	8/75 (10.7%)	11	4/35 (11.4%)	8
Ascites	7/75 (9.3%)	13	3/35 (8.6%)	3
Abdominal distension	6/75 (8%)	7	3/35 (8.6%)	3
Abdominal pain upper	9/75 (12%)	15	0/35 (0%)	0
Dyspepsia	7/75 (9.3%)	9	2/35 (5.7%)	2
Abdominal discomfort	6/75 (8%)	8	0/35 (0%)	0
Gastrooesophageal reflux	6/75 (8%)	8	0/35 (0%)	0
Malabsorption	4/75 (5.3%)	6	0/35 (0%)	0
Rectal haemorrhage	4/75 (5.3%)	4	0/35 (0%)	0
Mucosal inflammation	6/75 (8%)	8	1/35 (2.9%)	1
General disorders
Asthenia	34/75 (45.3%)	77	12/35 (34.3%)	46
Fatigue	19/75 (25.3%)	50	10/35 (28.6%)	24
Pyrexia	18/75 (24%)	30	2/35 (5.7%)	2
Oedema peripheral	12/75 (16%)	22	7/35 (20%)	9
Pain	5/75 (6.7%)	6	2/35 (5.7%)	2
Chills	6/75 (8%)	7	0/35 (0%)	0
Injection site reaction	5/75 (6.7%)	8	0/35 (0%)	0
Injection site pain	4/75 (5.3%)	6	0/35 (0%)	0
Oedema	4/75 (5.3%)	6	0/35 (0%)	0
Hepatobiliary disorders
Jaundice	9/75 (12%)	10	1/35 (2.9%)	1
Infections and infestations
Urinary tract infection	7/75 (9.3%)	10	3/35 (8.6%)	4
Nasopharyngitis	5/75 (6.7%)	8	1/35 (2.9%)	3
Respiratory tract infection	4/75 (5.3%)	6	0/35 (0%)	0
Investigations
Weight decrased	14/75 (18.7%)	17	1/35 (2.9%)	1
Platelet count decrased	7/75 (9.3%)	24	7/35 (20%)	14
Alanine aminotransferase increased	6/75 (8%)	15	2/35 (5.7%)	2
Neutrophil count decreased	5/75 (6.7%)	8	2/35 (5.7%)	3
Blood bilirubin increased	5/75 (6.7%)	12	1/35 (2.9%)	1
WBC count deceased	2/75 (2.7%)	7	4/35 (11.4%)	7
Aspartate aminotransferase increased	4/75 (5.3%)	11	1/35 (2.9%)	1
Blood alkaline phosphatase increased	4/75 (5.3%)	11	1/35 (2.9%)	2
Haemoglobin deceased	3/75 (4%)	10	2/35 (5.7%)	3
Vitamin D decreased	5/75 (6.7%)	6	0/35 (0%)	0
Blood potassium decreased	3/75 (4%)	10	2/35 (5.7%)	3
Metabolism and nutrition disorders
Decreased appetite	33/75 (44%)	45	11/35 (31.4%)	24
Vitamin D deficiency	7/75 (9.3%)	7	1/35 (2.9%)	1
Hypokalaemia	2/75 (2.7%)	3	3/35 (8.6%)	5
Musculoskeletal and connective tissue disorders
Back pain	17/75 (22.7%)	24	5/35 (14.3%)	6
Arthralgia	7/75 (9.3%)	9	2/35 (5.7%)	3
Nervous system disorders
Dysquesia	13/75 (17.3%)	17	2/35 (5.7%)	2
Lethargy	9/75 (12%)	15	1/35 (2.9%)	2
Dizziness	8/75 (10.7%)	9	1/35 (2.9%)	1
Headache	8/75 (10.7%)	9	0/35 (0%)	0
Parasthesia	4/75 (5.3%)	4	1/35 (2.9%)	1
Psychiatric disorders
Insomnia	9/75 (12%)	9	3/35 (8.6%)	4
Anxiety	9/75 (12%)	9	2/35 (5.7%)	4
Depression	5/75 (6.7%)	6	2/35 (5.7%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnoea	7/75 (9.3%)	10	3/35 (8.6%)	4
Cough	7/75 (9.3%)	11	1/35 (2.9%)	1
Epistaxis	1/75 (1.3%)	1	2/35 (5.7%)	2
Skin and subcutaneous tissue disorders
Pruritis	7/75 (9.3%)	8	2/35 (5.7%)	3
Dry skin	5/75 (6.7%)	6	3/35 (8.6%)	3
Rash	6/75 (8%)	10	2/35 (5.7%)	2
Alopecia	5/75 (6.7%)	6	2/35 (5.7%)	3

Limitations/Caveats

This proof of concept study was not formally sized to test a specific pre-defined efficacy hypothesis. However, it has provided important insights into the potential for efficacy improvements with the use of IMM-101 in combination with chemotherapy in advanced pancreatic cancer. Safety assessment based on AE & SAE profiles in each treatment arm had limitations as GEM is associated with frequent AEs and was given in both treatment arms. Thus, assessment of causality was difficult to interpret.

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Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.