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Colorectal CancerPhase 2SERPENTINENCT06680739

Single cEll pRofiling PErsistaNce To ImmuNothErapy

A Phase 2 study testing Durvalumab and Tremelimumab in people with Colorectal Cancer and Endometrial Cancer, run by Vall d'Hebron Institute of Oncology at 1 site in Spain.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The SERPENTINE trial (ESR 21-21165) is a phase II clinical study aiming to evaluate the efficacy of durvalumab and tremelimumab, alone or in combination, in patients with colorectal or endometrial cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Cancer, Endometrial Cancer
What is being tested?
Durvalumab and Tremelimumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteSpain
Study dates
1 Mar 2022to 1 Jul 2032
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and Accountability Act in the US, European Union [EU] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
  • Age > 18 years at time of study entry.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Cohort 1: histologically confirmed recurrent or metastatic CRC or endometrial cancer irrespective of prior treatment history with chemotherapy and/or targeted agents, not amenable to surgery and known tumor MSI-H or dMMR status per local standard of practice.
  • Cohort 2: histologically confirmed recurrent or metastatic CRC not amenable to surgery and known tumor MSS or pMMR status per local standard of practice, that have progressed during or after, at least 2 lines of fluoropyrimidine, irinotecan and/or oxaliplatin containing therapy with or without bevacizumab according to institutional practice or have not tolerated therapy for advanced/metastatic disease; if epidermal growth factor receptor (EGFR) positive/RAS wild type, prior anti-EGFR treatment is required. Or histologically confirmed recurrent or metastatic endometrial cancer that have progressed during or after a platinum and taxane-based regimen, not amenable to surgery and known tumor MSS or pMMR status per local standard of practice.
  • Life expectancy of > 12 weeks.
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  • Body weight >30 kg.
  • Adequate normal organ and marrow function as defined below:
  • Hemoglobin ≥9.0 g/dL
  • Absolute neutrophil count (ANC) 1.5 (or 1.0) x 109/L (> 1500 per mm3)
  • Platelet count ≥100 x 109/L (>75,000 per mm3)
  • Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
  • AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5 x ULN
  • Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.
  • Creatinine ≤1.5 x ULN OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCla) ≥60 mL/min for subject with creatinine levels >1.5 x institutional ULN. Creatinine clearance (CrCl) should be calculated per institutional standard.
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
  • Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
  • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
  • Have at least 1 tumoral lesion of minimum 10 mm in diameter that is suitable for initial biopsy.
  • Presence of at least 1 measurable lesion according to RECIST v1.1 apart from the lesion that is biopsiable before initiating treatment.
  • Male and Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 7.1 for the course of the trial and for 180 days after the last dose of durvalumab + tremelimumab combination therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the longer time period.

Who cannot join

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of treatment.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
  • Has had a prior anti-cancer mAb within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to mAbs administered more than 4 weeks earlier.
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  • Has had prior chemotherapy, targeted small molecule therapy, hormonal therapy or radiation therapy for cancer therapy within 2 weeks prior to study Day 1. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
  • Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria:
  • Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
  • Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study drug and patients must have recovered adequately from the eventual toxicity and/or complications related with the surgical procedure. Note: Local surgery of isolated lesions for palliative intent is acceptable.
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • History of allogenic organ transplantation.
  • Has known active CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  • Patients with celiac disease controlled by diet alone.
  • Has evidence of interstitial lung disease or a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy, also including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. The conditions also include uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
  • Has previously received prior therapy with an anti-PD-1, anti-PD-L1 including durvalumab, or anti CTLA-4 (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
  • Has received a live vaccine within 30 days of planned start of study therapy. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
  • Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions, and requirements.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Elena Elez, MD PhD contact

+34 932744350

meelez@vhio.net

Susana Muñoz contact

smunoz@vhio.net

Spain1 site, 1 recruiting

  • Vall d'Hebron Institute of Oncology

    Barcelona

    Elena Garralda, MD, 0034 93 489 30 00, egarralda@vhio.net

    Elena Garralda, MD

    Recruiting

Other trials in Spain

About this study

Official title: Single Cell Characterization of Persistent Cells Upon Treatment With Durvalumab (MEDI4736) With or Without Tremelimumab in MSS and MSI Colorectal and Endometrial Tumors: the SERPENTINE Clinical Trial

The SERPENTINE trial (ESR 21-21165) is a phase II clinical study aiming to evaluate the efficacy of durvalumab and tremelimumab, alone or in combination, in patients with colorectal or endometrial cancer. The trial targets patients with microsatellite instability-high (MSI-H) tumors and those with microsatellite stable (MSS) tumors.

Colorectal and endometrial cancers present significant challenges due to their heterogeneity and variable responses to treatment. Immunotherapy, particularly checkpoint inhibitors like durvalumab and tremelimumab, has shown promise in some patients, but predicting response remains elusive. The SERPENTINE trial aims to address this gap by investigating the effectiveness of these immunotherapies in a carefully selected patient population.

Read the detailed description

The trial is a single-center, open-label study with two cohorts: one for patients with MSI-H tumors and another for those with MSS tumors. Patients will be randomized to receive either durvalumab alone or in combination with tremelimumab. Tumor assessments will be conducted every 8 weeks using RECIST v1.1 criteria. Statistical analysis will employ descriptive statistics, and safety and efficacy data will be analyzed based on intention-to-treat principles.

Being tested
Durvalumab, Tremelimumab
Keywords
MSI cancer, MSS cancer
Medical subject headings
Colorectal Neoplasms, Endometrial Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DurvalumabDrug

    Durvalumab 1500 mg IV every 4 weeks

  • TremelimumabDrug

    Tremelimumab 300 mg IV as a single dose

Study groups in NCT06680739
Study groupRoleWhat they receive
Control armExperimentalPatients in this arm receive Durvalumab alone. Durvalumab is administered intravenously (IV) at a dose of 1500 mg every 4 weeks. This arm is designed to evaluate the efficacy and safety of Durvalumab monotherapy in patients with colorectal or endometrial cancer.
Receives: Drug: Durvalumab
MSI armExperimentalPatients in this arm receive a combination of Durvalumab and Tremelimumab. They initially receive Tremelimumab as a single dose of 300 mg IV, followed by Durvalumab administered at a dose of 1500 mg IV every 4 weeks. This arm aims to assess the efficacy and safety of combining Durvalumab with Tremelimumab in patients with colorectal or endometrial cancer.
Receives: Drug: Durvalumab; Drug: Tremelimumab
MSS armExperimentalPatients in this arm also receive a combination of Durvalumab and Tremelimumab. Similar to Cohorte 1B, they receive Tremelimumab as a single dose of 300 mg IV, followed by Durvalumab administered at a dose of 1500 mg IV every 4 weeks. However, patients in this arm have tumors with microsatellite stability (MSS), unlike Cohorte 1B where patients have tumors with microsatellite instability (MSI). This arm aims to evaluate the efficacy and safety of the Durvalumab and Tremelimumab combination in patients with MSS tumors.
Receives: Drug: Durvalumab; Drug: Tremelimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Evaluation of Objective Response Rate (ORR)

    Assess the objective response rate (ORR) of Durvalumab or Tremelimumab 300 mg single dose followed by Durvalumab in patients with microsatellite instable (MSI) colorectal cancer (CRC) or endometrial cancer (EC) and Tremelimumab 300 mg single dose followed by Durvalumab in refractory microsatellite stable (MSS) CRC and EC according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

    Measured: From treatment initiation until objective response confirmation or progression of disease (24 months).

Secondary outcomes (9)

  1. Antitumor Activity Assessment (PFS)

    Evaluate the antitumor activity of Durvalumab + Tremelimumab in MSS CRC/EC and MSI CRC/EC based on progression-free survival (PFS).

    Measured: Throughout the study duration (24 months).

  2. Antitumor Activity Assessment (OS)

    Evaluate the antitumor activity of Durvalumab + Tremelimumab in MSS CRC/EC and MSI CRC/EC based on overall survival (OS).

    Measured: Throughout the study duration (24 months).

  3. Antitumor Activity Assessment (DoR)

    Evaluate the antitumor activity of Durvalumab + Tremelimumab in MSS CRC/EC and MSI CRC/EC based on duration of response (DoR).

    Measured: Throughout the study duration (24 months).

  4. Antitumor Activity Assessment (TTMR)

    Evaluate the antitumor activity of Durvalumab + Tremelimumab in MSS CRC/EC and MSI CRC/EC based on time to maximum response (TTMR).

    Measured: Throughout the study duration (24 months).

  5. Antitumor Activity Assessment (irRR)

    Evaluate the antitumor activity of Durvalumab + Tremelimumab in MSS CRC/EC and MSI CRC/EC based on immune-related response rate (irRR)

    Measured: Throughout the study duration (24 months).

  6. Antitumor Activity Assessment (biomarkers)

    Evaluate the antitumor activity of Durvalumab + Tremelimumab in MSS CRC/EC and MSI CRC/EC based on genomic and immune biomarkers.

    Measured: Throughout the study duration (24 months).

  7. Single-Cell Characterization of Persistent Cells

    Characterize persistent cells upon treatment with Durvalumab in MSI CRC/EC and Durvalumab + Tremelimumab in MSS CRC/EC and MSI CRC/EC at a single-cell level.

    Measured: At baseline, at the time of maximal response, and at progression (48 months).

  8. Correlation of Antitumor Activity with Biomarkers

    Examine the correlation between the anti-tumor effects of Durvalumab and Durvalumab + Tremelimumab with additional biomarkers found in tumor tissue and blood samples.

    Measured: Throughout the study duration (24 months).

  9. Exploration of Immunotoxicity Biomarkers

    Explore biomarkers of immunotoxicity associated with Durvalumab and Durvalumab + Tremelimumab treatment.

    Measured: Throughout the study duration (24 months).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Nov 2024
  2. Study start1 Mar 2022
  3. Primary completion1 Jul 2032 (estimated)
  4. Study completion1 Jul 2032 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06680739
Sponsor's protocol ID
ESR 21-21165
Acronym
SERPENTINE
Status last verified
May 2026
First submitted
24 Apr 2024
Last updated
1 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Durvalumab and Tremelimumab in people with Colorectal Cancer and Endometrial Cancer, run by Vall d'Hebron Institute of Oncology at 1 site in Spain.

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 22 inclusion and 29 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: looking for participants now, as of the sponsor's last update on 1 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. 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 phase mean?

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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Elena Elez, MD PhD (+34 932744350, meelez@vhio.net), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluation of Objective Response Rate (ORR) (time frame: From treatment initiation until objective response confirmation or progression of disease (24 months).). 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 NCT06680739.

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 1 Jun 2026.

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