Description:
Phase I/II clinical trial investigates the safety, tolerability, immunogenicity and
preliminary efficacy of multiple doses of PolyPEPI1018 CRC vaccine as an add-on treatment to
the standard-of-care maintenance therapy in patients with metastatic colorectal cancer.
Clinical responses will be evaluated by indiction of T cell responses, T lymphocyte
infiltration in accessible biopsy sites, and by objective tumor responses. This study will
also explore the accuracy of the predicted T cell responses in each patient using the
candidate companion diagnostic test and the correlations between clinical responses and
predicted T cell responses.
Title
- Brief Title: Safety and Immunogenicity of PolyPEPI1018 Vaccine in the Treatment of Metastatic Colorectal Cancer (OBERTO)
- Official Title: Single Dose, Multi-center Study to Evaluate Safety, Tolerability and Immunogenicity of Subcutaneous Injection of PolyPEPI1018 Vaccine as an Add-on Immunotherapy to the Standard-of-Care Maintenance Therapy in Subjects With Metastatic Colorectal Cancer (CRC)
Clinical Trial IDs
- ORG STUDY ID:
OBERTO 101
- NCT ID:
NCT03391232
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Cancer Immunotherapy | | PolyPEPI1018 CRC Vaccine |
Purpose
TREOS' Phase I clinical trial will investigate the safety, tolerability, and immunogenicity
of a single dose of PolyPEPI1018 CRC Vaccine as an add-on treatment to the standard-of-care
maintenance therapy in patients with metastatic colorectal cancer. This study will also
explore the accuracy of prediction of pre-existing and newly induced CD8+ T cell responses in
each patient using the PEPI Test and T lymphocyte infiltration detected in accessible biopsy
sites.
Detailed Description
This is a Phase 1, open-label, single-arm, multicenter study to evaluate the safety,
tolerability, and immunogenicity of a single subcutaneous (SC) injection of PolyPEPI1018 as
an add-on immunotherapy to the standard-of-care maintenance therapy in approximately 10
subjects with mCRC.
The study is composed of a 3‑week Screening Period, the administration of a single dose
vaccine (Day 1, Week 0), and a 12‑week Follow‑up Period. The study will be conducted on an
outpatient basis.
Screening should be performed in parallel with the subject's completion of the
standard-of-care first-line treatment and initiation of the standard-of-care maintenance
treatment.
The single dose of PolyPEPI1018 will be administered after the subject initiates the
maintenance regimen, and within 3 weeks after the eligibility CT scan was performed (should
be performed at the completion of the first-line treatment).
Subjects will be monitored every 3 weeks for 12 weeks after administration of PolyPEPI1018
(i.e. Weeks 3, 6, 9 and 12).
Trial Arms
| Name | Type | Description | Interventions |
|---|
| PolyPEPI1018 CRC Vaccine | Experimental | The vaccine contains 6 synthetic peptides mixed with the adjuvant Montanide™. The peptides were selected to induce T cell responses against 12 epitopes from 7 cancer testis antigens (CTAs), which are the most frequently expressed CTAs in colorectal cancer. The 6 peptides were optimized with the PEPI biomarker to induce long lasting CRC specific T cell responses. | |
Eligibility Criteria
Inclusion Criteria:
1. Male or female subjects, 18-75 years of age at time of Screening who provide written
informed consent prior to initiation of any study procedure
2. Histologically confirmed metastatic adenocarcinoma originating from the colon or the
rectum
3. Presence of at least 1 measurable reference lesion according to the Response
Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
4. Experienced PR or stable disease during first‑line treatment with a systemic
chemotherapy regimen and 1 biological therapy regimen
5. Maintenance therapy with 1 biological therapy regimen with or without a systemic
chemotherapy regimen scheduled to initiate prior to the first day of treatment with
the study drug
6. No more than 1 line of chemotherapy regimen for mCRC (adjuvant therapy for
non-metastasized disease is allowed if terminated more than 6 months before Screening
and without recurrence within 6 months after the end of adjuvant treatment)
7. Last CT scan at 3 weeks or less before the first day of treatment
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
9. Women of childbearing potential must agree to appropriately use an effective form of
contraception (failure rate of <1% per year) for 3 months from the day of the
treatment. An effective form of contraception is defined as using hormonal
contraceptives or an intrauterine device combined with at least 1 of the following
forms of contraception: a diaphragm, cervical cap or condom
10. Men must agree to use an effective form of contraception (as defined above), and not
donate sperm for 3 months from the day of the treatment
11. White blood cell count ≥3.0 × 109/L with neutrophils ≥1.5 × 109/L
12. Platelets ≥100 × 109/L, hemoglobin ≥5.6 mmol/L (corresponding to 9 g/dL)
13. Serum bilirubin ≤1.5 × upper limit of normal (ULN) set by the site
14. Alanine amino transferase (ALAT) and aspartate amino transferase (ASAT) ≤2.5 × ULN in
the absence of liver metastases. ALAT and ASAT ≤5 × ULN set by the site in the
presence of liver metastases
15. Serum creatinine ≤1.5 × ULN set by the site and creatinine clearance >30 mL/min using
Cockroft formula
16. Relevant toxicities of prior therapies must have resolved, except for
oxaliplatin-related neuropathy or alopecia
17. Anticipated life expectancy ≥6 months Subject is willing and able to comply with the
requirements of the protocol
Exclusion Criteria:
1. Received chronic systemic immune therapy or immunosuppressant medication other than
steroids within the last 6 weeks prior to start of study treatment
2. Received continuous systemic steroid treatment within the last 2 weeks prior to start
of study treatment
3. Colorectal cancer with documented high microsatellite instability (MSI‑H)
4. Colorectal cancer with documented BRAF mutations
5. Pre-existing systemic autoimmune or antibody-mediated diseases or immune deficiency
diseases
6. Central nervous system (CNS) metastases
7. Active or uncontrolled severe infections or undiagnosed febrile condition >38ºC
8. Acute or subacute intestinal obstruction or history of chronic intestinal inflammatory
diseases
9. Symptomatic peritoneal carcinomatosis
10. Peritonitis
11. Serious, non-healing wounds, ulcers or bone fractures
12. Nephrotic syndrome
13. Arterial thromboembolisms or severe hemorrhages within 6 months before study enrolment
(except bleeding tumor before tumor resection surgery)
14. Hemorrhagic diathesis or thrombotic tendency
15. Major surgery or radiotherapy within 12 weeks prior to the study treatment or
anticipation of needing such procedure during the study period
16. Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated
drainage more than once every 28 days
17. Participants with active malignancy (other than colorectal cancer) or a prior
malignancy within the past 12 months
18. Participant with myocardial infarction within 6 months prior to enrollment or New York
Heart Association Class III or IV heart failure, uncontrolled angina, severe
uncontrolled ventricular arrhythmias or electrocardiographic evidence of acute
ischemia or active conduction system abnormalities. Prior to the first dose of study
treatment, any electrocardiogram (ECG) abnormality at Screening must be documented by
the investigator as not medically relevant
19. Administration of a live, attenuated vaccine within 4 weeks before randomization or
anticipation of a live attenuated vaccine will be required during the study
20. Participant has participated in another clinical study involving an investigational
product (IP) or investigational device within 30 days prior to enrollment or is
scheduled to participate in another clinical study involving an IP or investigational
device during the course of this study
21. Known hypersensitivity to any component of the investigational drug
22. If female, participant is pregnant (exclusion confirmed with beta-human chorionic
gonadotropin [hCG] test) or lactating at the time of enrollment, or has plans to
become pregnant or start breastfeeding during the study
23. Pre-existing alcohol or drug abuse
24. Medical or mental impairments which make it impossible to obtain the patient's consent
or to conduct the study
25. A significant concomitant medical condition which the clinical investigator believes
precludes the patient from enrolling in the study Absent or limited legal competence
| Maximum Eligible Age: | 75 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Incidence of Treatment Related Adverse Events |
| Time Frame: | 21 days |
| Safety Issue: | |
| Description: | Occurrence of at least 1 ≥Grade 4 local adverse event (AE) or 1 ≥Grade 3 systemic AE and/or signs/symptoms, lab toxicities, and/or clinical events that is probably or definitely related to study treatment |
Secondary Outcome Measures
| Measure: | Prediction of T cell responses |
| Time Frame: | 21 days |
| Safety Issue: | |
| Description: | To determine epitopes of PolyPRPI1018 capable of inducing T cell responses in each study subject |
| Measure: | Measure T cell responses |
| Time Frame: | 12 weeks |
| Safety Issue: | |
| Description: | To measure epitope specific T cell responses in each study subjects |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Treos Bio Zrt |
Last Updated
April 11, 2018
