Colorectal CancerPhase 1/2OBERTONCT03391232
PolyPEPI1018 Vaccine and CDx for the Treatment of Metastatic Colorectal Cancer (OBERTO)
A Phase 1/2 study testing PolyPEPI1018 CRC Vaccine in people with Colorectal Cancer, run by Treos Bio Zrt at 2 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- PolyPEPI1018 CRC Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 3 May 2018to 17 Jul 2019
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- Histologically confirmed metastatic adenocarcinoma originating from the colon or the rectum
- Presence of at least 1 measurable reference lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
- Experienced PR or stable disease during first-line treatment with a systemic chemotherapy regimen and 1 biological therapy regimen
- Maintenance therapy with a fluoropyrimidine (5-fluorouracil or capecitabine) plus the same biologic agent (bevacizumab, cetuximab or panitumumab) used during induction, scheduled to initiate prior to the first day of treatment with the study drug
- 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)
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- Last CT scan at 3 weeks or less before the first day of treatment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- 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
- 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
- White blood cell count ≥3.0 × 109/L with neutrophils ≥1.5 × 109/L
- Platelets ≥100 × 109/L, hemoglobin ≥5.6 mmol/L (corresponding to 9 g/dL)
- Serum bilirubin ≤1.5 × upper limit of normal (ULN) set by the site
- 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
- Serum creatinine ≤1.5 × ULN set by the site and creatinine clearance >30 mL/min using Cockroft formula
- Relevant toxicities of prior therapies must have resolved, except for oxaliplatin-related neuropathy or alopecia
- Anticipated life expectancy ≥6 months Subject is willing and able to comply with the requirements of the protocol
Who cannot join
- Received chronic systemic immune therapy or immunosuppressant medication other than steroids within the last 6 weeks prior to start of study treatment
- Received continuous systemic steroid treatment within the last 2 weeks prior to start of study treatment
- Colorectal cancer with documented high microsatellite instability (MSI-H)
- Colorectal cancer with documented BRAF mutations
- Pre-existing systemic autoimmune or antibody-mediated diseases or immune deficiency diseases
- Central nervous system (CNS) metastases
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- Active or uncontrolled severe infections or undiagnosed febrile condition >38ºC
- Acute or subacute intestinal obstruction or history of chronic intestinal inflammatory diseases
- Symptomatic peritoneal carcinomatosis
- Peritonitis
- Serious, non-healing wounds, ulcers or bone fractures
- Nephrotic syndrome
- Arterial thromboembolisms or severe hemorrhages within 6 months before study enrolment (except bleeding tumor before tumor resection surgery)
- Hemorrhagic diathesis or thrombotic tendency
- Major surgery or radiotherapy within 12 weeks prior to the study treatment or anticipation of needing such procedure during the study period
- Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage more than once every 28 days
- Participants with active malignancy (other than colorectal cancer) or a prior malignancy within the past 12 months
- 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
- Administration of a live, attenuated vaccine within 4 weeks before randomization or anticipation of a live attenuated vaccine will be required during the study
- 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
- Known hypersensitivity to any component of the investigational drug
- 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
- Pre-existing alcohol or drug abuse
- Medical or mental impairments which make it impossible to obtain the patient's consent or to conduct the study
- A significant concomitant medical condition which the clinical investigator believes precludes the patient from enrolling in the study Absent or limited legal competence
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Safety, Tolerability, Immunogenicity and Efficacy of Multiple PolyPEPI1018 Vaccinations as an Add-on Immunotherapy to the Standard-of-Care Maintenance Therapy in Subjects With Metastatic Colorectal Cancer
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.
Read the detailed description
This is a Phase I/II, open-label, single-arm, multicenter study to evaluate the safety, tolerability, immunogenicity and efficacy of a multiple subcutaneous injection of PolyPEPI1018 as an add-on immunotherapy to the standard-of-care maintenance therapy in approximately 15 subjects with metastatic colorectal cancer.
The first part of the study investigates the administration of a single vaccine dose during 12-week follow-up period on an outpatient basis. Screening is 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. A single dose of PolyPEPI1018 is administered after the subject initiates the maintenance regimen, and within 3 weeks after the eligibility CT scan was performed. Subjects are monitored every 3 weeks for 12 weeks.
The second part of the study investigates the administration of 3 vaccine doses (Weeks 0, 13, 26) then 12 weeks follow-up on an outpatient basis.
- Conditions
- Colorectal Cancer
- Being tested
- PolyPEPI1018 CRC Vaccine
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PolyPEPI1018 CRC VaccineBiological
Colorectal Cancer Vaccine
| Study group | Role | What they receive |
|---|---|---|
| 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 dominant epitopes from 7 cancer testis antigens (CTAs), which are the most frequently expressed CTAs in colorectal cancer. The 6 peptides were optimized to induce long lasting CRC specific T cell responses. Receives: Biological: PolyPEPI1018 CRC Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Related Adverse Events
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
Measured: from 1st vaccination to 21 days after last vaccinations, up to 41 weeks
Secondary outcomes (2)
Number of Participants Having T Cell Immune Response
Measured CD4+ and CD8+ T cell responses from each subject for each antigen of the vaccine
Measured: 12 weeks
Number of Predicted Antigen Specific T Cell Responses Per Patient
Epitopes restricted to multiple HLA class I alleles (Personal Epitope, PEPI) of a subject were predicted. PEPIs determined for each vaccine antigen can predict the antigen-specific T cell responses for each patient.
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2018
- Study start3 May 2018
- Primary completion17 Jul 2019
- Study completion17 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Treos Bio Zrt
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Mayo Clinic, University of Pisa, Laboratory Corporation of America, PPD Development, LP, ImmunXperts SA
- Responsible party
- Sponsor
- Investigators
- Eva Vegh, MD, MDA, Study chair, Treos Bio Zrt
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03391232
- Sponsor's protocol ID
- OBERTO 101
- Acronym
- OBERTO
- Status last verified
- May 2022
- First submitted
- 19 Dec 2017
- Last updated
- 26 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hubbard JM, Toke ER, Moretto R, Graham RP, Youssoufian H, Lorincz O, Molnar L, Csiszovszki Z, Mitchell JL, Wessling J, Toth J, Cremolini C. Safety and Activity of PolyPEPI1018 Combined with Maintenance Therapy in Metastatic Colorectal Cancer: an Open-Label, Multicenter, Phase Ib Study. Clin Cancer Res. 2022 Jul 1;28(13):2818-2829. doi: 10.1158/1078-0432.CCR-22-0112.
PubMed 35472243
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Tolerability, Immunogenicity and Efficacy of Multiple PolyPEPI1018 Vaccinations as an Add-on Immunotherapy to the Standard-of-Care Maintenance Therapy in Subjects With Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT03391232
- Acronym / sponsor ID
- OBERTO / OBERTO 101
- Conditions
- Colorectal Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Treos Bio ZrtIndustry (pharma, biotech, devices)
- Collaborators
- Mayo Clinic, University of Pisa, Laboratory Corporation of America, PPD Development, LP, ImmunXperts SA
- Study start
- 3 May 2018 (actual)
- Primary completion
- 17 Jul 2019 (actual)
- Study completion
- 17 Jul 2019 (actual)
- First posted
- 5 Jan 2018 (actual)
- Results
- Posted 14 Apr 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a Phase I/II, open-label, single-arm, multicenter study to evaluate the safety, tolerability, immunogenicity and efficacy of a multiple subcutaneous injection of PolyPEPI1018 as an add-on immunotherapy to the standard-of-care maintenance therapy in approximately 15 subjects with metastatic colorectal cancer.
The first part of the study investigates the administration of a single vaccine dose during 12-week follow-up period on an outpatient basis. Screening is 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. A single dose of PolyPEPI1018 is administered after the subject initiates the maintenance regimen, and within 3 weeks after the eligibility CT scan was performed. Subjects are monitored every 3 weeks for 12 weeks.
The second part of the study investigates the administration of 3 vaccine doses (Weeks 0, 13, 26) then 12 weeks follow-up on an outpatient basis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PolyPEPI1018 CRC Vaccine | Experimental | Biological: PolyPEPI1018 CRC VaccineThe vaccine contains 6 synthetic peptides mixed with the adjuvant Montanide™. The peptides were selected to induce T cell responses against 12 dominant epitopes from 7 cancer testis antigens (CTAs), which are the most frequently expressed CTAs in colorectal cancer. The 6 peptides were optimized to induce long lasting CRC specific T cell responses. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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
- Histologically confirmed metastatic adenocarcinoma originating from the colon or the rectum
- Presence of at least 1 measurable reference lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
- Experienced PR or stable disease during first-line treatment with a systemic chemotherapy regimen and 1 biological therapy regimen
- Maintenance therapy with a fluoropyrimidine (5-fluorouracil or capecitabine) plus the same biologic agent (bevacizumab, cetuximab or panitumumab) used during induction, scheduled to initiate prior to the first day of treatment with the study drug
Key exclusion criteria (25 listed)
- Received chronic systemic immune therapy or immunosuppressant medication other than steroids within the last 6 weeks prior to start of study treatment
- Received continuous systemic steroid treatment within the last 2 weeks prior to start of study treatment
- Colorectal cancer with documented high microsatellite instability (MSI-H)
- Colorectal cancer with documented BRAF mutations
- Pre-existing systemic autoimmune or antibody-mediated diseases or immune deficiency diseases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PolyPEPI1018 CRC VaccineColorectal Cancer Vaccine | Biological | PolyPEPI1018 CRC Vaccine |
Primary outcome
Number of Participants With Treatment Related Adverse Events
Time frame: from 1st vaccination to 21 days after last vaccinations, up to 41 weeks
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
2 secondary outcomes
Number of Participants Having T Cell Immune Response
Time frame: 12 weeks
Number of Predicted Antigen Specific T Cell Responses Per Patient
Time frame: 21 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35472243Hubbard JM, Toke ER, Moretto R, Graham RP, Youssoufian H, Lorincz O, Molnar L, Csiszovszki Z, Mitchell JL, Wessling J, Toth J, Cremolini C. Safety and Activity of PolyPEPI1018 Combined with Maintenance Therapy in Metastatic Colorectal Cancer: an Open-Label, Multicenter, Phase Ib Study. Clin Cancer Res. 2022 Jul 1;28(13):2818-2829. doi: 10.1158/1078-0432.CCR-22-0112.
- Treos Bio uses novel biomarkers to develop personalized and off-the-shelf cancer vaccinesLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eva Vegh, MD, MDA study chair
Treos Bio Zrt
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PolyPEPI1018 CRC Vaccine in people with Colorectal Cancer, run by Treos Bio Zrt at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment Related Adverse Events (time frame: from 1st vaccination to 21 days after last vaccinations, up to 41 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03391232, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2022.