Antigen-specific Cancer Immunotherapy (TG01) and Gemcitabine as Adjuvant Therapy in Resected Pancreatic Cancer

• ClinicalTrials.gov Identifier: NCT02261714
• Recruitment Status: Completed
• First Posted: October 10, 2014
• Results First Posted: May 14, 2020
• Last Update Posted: May 14, 2020
• Sponsor: Targovax ASA
• Information provided by (Responsible Party): Targovax ASA

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pancreatic Cancer, Resected
• Intervention: Biological: TG01
• Enrollment: 32

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	TG01/GM-CSF and Gemcitabine
Arm/Group Description	TG01: TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment. TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections. Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes TG01: For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surge
Period Title: Overall Study
Started	32
Completed	4
Not Completed	28

Baseline Characteristics

Arm/Group Title		TG01/GM-CSF and Gemcitabine
Arm/Group Description		TG01: TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment. TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections. Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes TG01: For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surge
Overall Number of Baseline Participants		32
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	32 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	16 50.0%
	>=65 years	16 50.0%
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	32 participants
		64.1; (46 to 79)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	32 participants
	Female	11 34.4%
	Male	21 65.6%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	32 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	31 96.9%
	More than one race	0 0.0%
	Unknown or Not Reported	1 3.1%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	32 participants
Norway		11
United Kingdom		21

Outcome Measures

1. Primary Outcome

Title	Patients' Safety During Study
Description	Assess the safety (number and nature of Adverse events and laboratory data occurring during study (before, during and after chemotherapy is given) in subjects treated with the Pancreatic Cancer ASCI
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TG01/GM-CSF and Gemcitabine
Arm/Group Description:	TG01: TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment. TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections. Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes TG01: For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surge
Overall Number of Participants Analyzed	32
Measure Type: Number; Unit of Measure: Events related to TG01 and /or GM-CSF
AEs related to TG01 and/or GM-CSF	90
SAEs related to TG01 and/or GM-CSF	2

2. Primary Outcome

Title	Patients' Immune Response
Description	Assess the Immune response (DTH responses and Proliferative T-cell responses) up to 2 years of treatment
Time Frame	During the 2 years of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TG01/GM-CSF and Gemcitabine
Arm/Group Description:	TG01: TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment. TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections. Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes TG01: For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surgery.
Overall Number of Participants Analyzed	32
Measure Type: Number; Unit of Measure: percentage of patients
	94

3. Secondary Outcome

Title	Clinical Efficacy
Description	Efficacy exploring disease free survival and overall survival.
Time Frame	DFS was followed for up to 2 years and OS until last patient included had been in the study for 3 years.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	TG01/GM-CSF and Gemcitabine
Arm/Group Description:	TG01: TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment. TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections. Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes TG01: For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surge
Overall Number of Participants Analyzed	32
Median (Full Range); Unit of Measure: Months
Overall survival	33.3; (24.0 to 40.0)
Disease free survival	16.1; (11.1 to 19.6)

4. Other Pre-specified Outcome

Title	Relationship Between (KRAS) Status and Clinical Efficacy
Description	Relationship between KRAS status and recurrence
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

As the majority of the patients (26 of 32) patients had a KRAS mutation detected, it was not possible to accurately assess relationship between KRAS status and survival outcomes.

Arm/Group Title	TG01/GM-CSF and Gemcitabine
Arm/Group Description:	TG01: TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment. TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections. Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes TG01: For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surgery.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	2 years
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	TG01/GM-CSF and Gemcitabine
Arm/Group Description	TG01: TG01 and GM-CSF will be administered on days 1, 8, 15, 22 and 36. TG01 alone will also be given on days 36 and 50 for DTH assessment. Gemcitabine will start at least 3 weeks after TG01/GM-CSF and will be given on days 1, 8 and 15 of a four-weeks cycle up to 6 cycles in total. Once chemotherapy is completed, GM-CSF and TG01 injections will resume and will be given every 4 weeks from the end of the chemotherapy period up to week 52 (plus once at week 5 post-chemotherapy) and then every 12 weeks from week 52 to week 104. TG01 alone will be given 8 weeks after the end of chemotherapy for DTH assessment. TG01 will be given at a dose of 0.70 mg/injection and GM-CSF will be given at a dose of 30 micrograms both as intradermal injections. Gemcitabine will be given at a dose of 1000 mg/m2 iv over 30 minutes TG01: For patients not able to start TG01 quickly after surgery, the vaccination can start at the same time as the chemotherapy as long as they start within 12 weeks from surgery.
All-Cause Mortality
	TG01/GM-CSF and Gemcitabine
	Affected / at Risk (%)
Total	18/32 (56.25%)
Serious Adverse Events
	TG01/GM-CSF and Gemcitabine
	Affected / at Risk (%)	# Events
Total	3/32 (9.38%)
General disorders
Pyrexia *	1/32 (3.13%)	2
Immune system disorders
Anaphylactic reaction *	2/32 (6.25%)	2
* Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	TG01/GM-CSF and Gemcitabine
	Affected / at Risk (%)	# Events
Total	16/32 (50.00%)
Gastrointestinal disorders
Nausea *	16/32 (50.00%)	43
* Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.

Results Point of Contact

• Name/Title: Chief Medical Officer
• Organization: Targovax ASA
• Phone: 004721398810
• EMail: contact@targovax.com

Publications:

Gjertsen MK, Buanes T, Rosseland AR, Bakka A, Gladhaug I, Soreide O, Eriksen JA, Moller M, Baksaas I, Lothe RA, Saeterdal I, Gaudernack G. Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma. Int J Cancer. 2001 May 1;92(3):441-50. doi: 10.1002/ijc.1205.

Weden S, Klemp M, Gladhaug IP, Moller M, Eriksen JA, Gaudernack G, Buanes T. Long-term follow-up of patients with resected pancreatic cancer following vaccination against mutant K-ras. Int J Cancer. 2011 Mar 1;128(5):1120-8. doi: 10.1002/ijc.25449.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Palmer DH, Valle JW, Ma YT, Faluyi O, Neoptolemos JP, Jensen Gjertsen T, Iversen B, Amund Eriksen J, Moller AS, Aksnes AK, Miller R, Dueland S. TG01/GM-CSF and adjuvant gemcitabine in patients with resected RAS-mutant adenocarcinoma of the pancreas (CT TG01-01): a single-arm, phase 1/2 trial. Br J Cancer. 2020 Mar;122(7):971-977. doi: 10.1038/s41416-020-0752-7. Epub 2020 Feb 17.

• Responsible Party: Targovax ASA
• ClinicalTrials.gov Identifier: NCT02261714
• Other Study ID Numbers: CT TG01-01
• First Submitted: March 24, 2014
• First Posted: October 10, 2014
• Results First Submitted: April 8, 2020
• Results First Posted: May 14, 2020
• Last Update Posted: May 14, 2020