Exploratory Study of TG02-treatment as Monotherapy or in Combination With Pembrolizumab to Assess Safety and Immune Activation in Patients With Locally Advanced Primary and Recurrent Oncogenic RAS Exon 2 Mutant Colorectal Cancer

NCT02933944 | Terminated Phase 1 Results

• 1 other identifier: CT TG02-01
• Study Type: interventional
• Target: 6
• Locations: 2 countries
• Sites: 4

Brief Summary

The purpose of this study is to determine safety and anti-tumor immune activation generated by TG02 and Granulocyte macrophage colony stimulating factor (GM-CSF), first as monotherapy (Part I), thereafter in combination with the checkpoint inhibitor pembrolizumab (Part II), in patients with locally advanced primary and recurrent colorectal cancer scheduled to have surgery. Part I will include 4-6 patients and Part II will include up to 10 patients. Part I and Part II are separate and independent sequential components of the study. Patients will only be able to participate in either the Part I cohort or Part II cohort. Main objective of the study is to investigate safety and immune response after TG02-treatment.

Conditions

Rectal Cancer

Keywords

locally recurrent

Outcome Measures

Primary Outcomes (4)

• Patients Safety During Study

  Safety of TG02-treatment by assessment of laboratory parameters (routine haematology and biochemistry), vital signs and recording of adverse events

  From start of study until End of study, which is approximately 4 weeks after surgery and maximum 20 weeks after start of TG02-treatment

• Patients' Immune Response Assessed by Delayed Type Hypersensitive (DTH) Test

  Number of patients with systemic TG02 specific immune response assessed by a Delayed Type Hypersensitivity (DTH) test

  8 weeks

• Systemic Immune Response: T-cell Response

  Systemic immune response assessed as change in presence of TG02 specific T-cells in peripheral blood

  8 weeks

• Immunological Activation in Tumour Mass by Assessing Number of Patients With Increased Intra-tumoural Lymphocytes.

  Immunological activation in tumour mass by assessing fold changes from baseline of intra-tumoural lymphocytes.

  8 weeks

Secondary Outcomes (4)

• Change of Immune Suppression Factors e.g. PD-1 and T-reg From Pre to Post Treatment

  8 weeks

• Change in Pathological Responses and Markers of Apoptosis in Tumour Tissue

  8 weeks

• Changes in Standard Uptake Values (SUV) Will be Assessed by FDG PET-CT Images

  From screening until surgery

• Changes in the Tumour Marker Carcinoembryonic Antigen (CEA) Throughout Treatment Will be Assessed by Analysis of Blood Samples to Follow the Evolution of Disease Under Treatment

  From screening until surgery

Study Arms (1)

TG02-treatment

EXPERIMENTAL

Part I: The TG02-treatment consists of an intradermal injection of GM-CSF followed by an injection of TG02. The GM-CSF is to be given 15-30 minutes before TG02. TG02-treatment will be administered on Days 1, 8, 15, 22 and 36. If surgery after week 10, TG02-treatment will also be given at week 10 (Day 64). Part II: TG02-treatment will be given as described under Part I. In addition pembrolizumab will be administered.

Biological: TG02-treatment; Drug: Pembrolizumab

Interventions

TG02-treatment BIOLOGICAL

TG02-treatment

Pembrolizumab DRUG

TG02-treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with locally advanced primary and recurrent colorectal cancer (CRC) (histologically or cytologically confirmed adenocarcinoma), with a confirmed oncogenic KRAS exon 2, codon 12 or 13 mutations, eligible for radical pelvic surgery at time of enrolment.
• Patient is ≥18 years of age and able to consent
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• Patient has adequate organ and bone marrow function within 28 days of study
• Neutrophil count \>1.5 x10\^9/L
• Platelets \>100 x10\^9/L
• Hb \>90g/L
• Total bilirubin \<1.5 upper limit of normal, ULN
• ALT and AST \<3.0 x ULN
• Serum creatinine \<3 x ULN or Creatinine Clearance ≥ 30ml/min (Cockroft-Gault or Nuclear GFR method)
• PT and APTT \<1.3 x ULN
• The patient is willing and able to comply with the protocol, and agrees to return to the hospital for study visits and examinations
• The patient has been fully informed about the study and is willing to participate in the study, and has provided written informed consent form prior to any trial specific screening procedures.

You may not qualify if:

• The patient has previously received an anticancer vaccine or immune checkpoint inhibitor, or participated in a trial involving the use of an anticancer vaccine or immune checkpoint inhibitor
• Patients where pre-surgery radiotherapy, chemotherapy or other anti-cancer therapy has not been completed ≥ 2 weeks prior to TG02-treatment
• The patients is receiving anti-cancer therapy for concurrent illness
• The patient has had a prior different malignancy within the last 3 years (excluding adequately treated basal cell or squamous cell carcinoma of the skin cancer, or localised low grade tumours considered cured and not requiring systemic therapy)
• The patient has uncontrolled or significant intercurrent or recent illness including:
• auto-immune disorder or history of autoimmune disease requiring immunosuppressive treatment.
• cardiac disorder such as uncontrolled cardiac failure, unstable angina or non-ST segment elevation myocardial infarction (NSTEMI) or myocardial infarction, uncontrolled arrhythmia less than 3 months before screening
• stroke or thromboembolic event within 3 months of study commencement
• active or uncontrolled severe infection
• history of solid organ transplantation or any condition requiring chronic treatment with corticosteroids or other immunosuppressive agents
• active coagulopathy/bleeding diathesis
• cirrhosis, chronic active or untreated persistent hepatitis
• history of adverse reactions to peptide vaccines
• The patient is pregnant or lactating.
• Has received an investigational drug within 4 weeks prior to study drug administration, or unless other has been agreed with the medical monitor

Sponsors & Collaborators

• Targovax ASA: lead

Study Sites (4)

Royal Brisbane & Women's Hospital (RBWH)

Brisbane, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Australia

Location

Auckland City Hospital

Auckland, New Zealand

Location

Christchurch Hospital

Christchurch, New Zealand

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Targovax

contact@targovax.com

+ 47 21398810

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2016
• First Posted: October 14, 2016
• Study Start: September 1, 2016
• Primary Completion: February 1, 2019
• Study Completion: September 1, 2019
• Last Updated: January 26, 2022
• Results First Posted: January 26, 2022

Record last verified: 2019-06

Locations

AU (2); NZ (2)