Single cEll pRofiling PErsistaNce To ImmuNothErapy

NCT06680739 | Recruiting Phase 2

• 1 other identifier: ESR 21-21165
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Colorectal Cancer; Endometrial Cancer

Keywords

MSI cancer; MSS cancer

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (9)

• Antitumor Activity Assessment (PFS)

  Throughout the study duration (24 months).

• Antitumor Activity Assessment (OS)

  Throughout the study duration (24 months).

• Antitumor Activity Assessment (DoR)

  Throughout the study duration (24 months).

• Antitumor Activity Assessment (TTMR)

  Throughout the study duration (24 months).

• Antitumor Activity Assessment (irRR)

  Throughout the study duration (24 months).

Study Arms (3)

Control arm

EXPERIMENTAL

Patients 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.

Drug: Durvalumab

MSI arm

EXPERIMENTAL

Patients 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.

Drug: Durvalumab; Drug: Tremelimumab

MSS arm

EXPERIMENTAL

Patients 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.

Drug: Durvalumab; Drug: Tremelimumab

Interventions

Durvalumab DRUG

Durvalumab 1500 mg IV every 4 weeks

Control arm; MSI arm; MSS arm

Tremelimumab DRUG

Tremelimumab 300 mg IV as a single dose

MSI arm; MSS arm

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• 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

Sponsors & Collaborators

• Vall d'Hebron Institute of Oncology: lead

Study Sites (1)

Vall d'Hebron Institute of Oncology

Barcelona, Spain

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Endometrial Neoplasms

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Elena Elez, MD PhD

  Vall d'Hebron Institute of Oncology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elena Elez, MD PhD

CONTACT

+34 932744350; meelez@vhio.net

Susana Muñoz

CONTACT

smunoz@vhio.net

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2024
• First Posted: November 8, 2024
• Study Start: March 1, 2022
• Primary Completion: September 1, 2025
• Study Completion: December 1, 2025
• Last Updated: November 8, 2024

Record last verified: 2024-11

Locations

ES (1)