Sotorasib Combined With First-line Chemotherapy for Advanced Pancreatic Adenocarcinoma

NCT06892054 | Recruiting Phase 1 DMC

• 2 other identifiers: TTD-24-012024-516233-12-00
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 26

Brief Summary

The main objective of this trial is to evaluate the safety and tolerability of sotorasib combined with first-line chemotherapy for advanced pancreatic adenocarcinoma harboring KRAS p.G12C mutation.

Conditions

Pancreatic Adenocarcinoma

Keywords

Pancreatic; sotorasib; TTD-24-01; KRASG12C

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety and tolerability of sotorasib combined with first-line chemotherapy for locally advanced or metastatic pancreatic adenocarcinoma harboring KRAS p.G12C mutation.

  Incidence of treatment-emergent adverse events (TEAEs) and related TEAEs (TRAEs) according to CTCAE V5.0.

  60 months

Secondary Outcomes (6)

• To evaluate the progression-free survival assessed by CT or MRI using RECIST 1.1 criteria of first-line chemotherapy combined with sotorasib for advanced pancreatic adenocarcinoma harboring KRAS p.G12C mutation

  60 months

• To evaluate the overall survival of first-line chemotherapy combined with sotorasib for advanced pancreatic adenocarcinoma harboring KRAS p.G12C mutation.

  60 months

• Overall response (OR)

  60 months

• Disease control (DC)

  60 months

• Duration of response (DOR)

  60 months

Study Arms (1)

First-line chemotherapy (gem/nab-P or FOLFIRINOX) combined with sotorasib

EXPERIMENTAL

A minimum of 6 and a maximum of 15 patients will be enrolled to receive first-line chemotherapy (gem/nab-P or mFOLFIRINOX at investigator choice) in combination with sotorasib 960 mg daily (QD).mFOLFIRINOX is recommended for patients with ECOG PS of 0 to 1, favourable comorbidity profile, patient preference and a support system for aggressive medical therapy, and access to chemotherapy port and infusion pump management services. Gem/nab-P is recommended for patients with ECOG PS of 0 to 1, a relatively favourable comorbidity profile, and patient preference and a support system for relatively aggressive medical therapy. Gem/nab-P is therefore the preferred first line treatment for patients expected to be intolerant to mFOLFIRINOX.

Drug: Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days)

Interventions

Sotorasib, 960 mg, oral daily dose for 4 weeks (28 days) DRUG

A minimum of 6 and a maximum of 15 patients will be enrolled to receive first-line chemotherapy (gem/nab-P or mFOLFIRINOX at investigator choice) in combination with sotorasib 960 mg daily (QD). The treatment with gem/nab-P and mFOLFIRINOX should be managed as per clinical practice.

Also known as: Lumykras

First-line chemotherapy (gem/nab-P or FOLFIRINOX) combined with sotorasib

Eligibility Criteria

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

You may qualify if:

• \) Willing and able to provide informed consent. 2) Men or women aged ≥ 18 years old. 3) Using effective contraceptive measures or sexual abstinence during the treatment, up to 7 days after the last dose of sotorasib, for at least 6 months after the last dose of gem/nab-P and for 15 months after the last dose of mFOLFIRINOX for woman of childbearing age and 12 months after stopping mFOLFIRINOX for men:
• Female of childbearing potential using a highly effective method of contraception (i.e., a method with less than 1% failure rate \[e.g., sterilization, hormone implants, hormone injections, some intrauterine devices, or vasectomized partner\])
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (without granulocyte colony-stimulating factor support within 2 weeks of laboratory test used to determine eligibility)
• Hemoglobin ≥ 9.0 g/dL (without transfusion within 2 weeks of laboratory test used to determine eligibility)
• Platelet count ≥ 100 x 109/L (without transfusion within 2 weeks of laboratory test used to determine eligibility)
• Aspartate aminotransferase (AST) and ALT ≤ 2.5 times the upper limit of normal (ULN) or ≤5 times if liver metastasis
• Serum bilirubin ≤ 1.5 x ULN
• International normalized ratio (INR) ≤ 1.5 x ULN. Prothrombin time (PT) ≤ 1.5 x ULN may be used instead of INR for sites whose laboratory do not report INR
• Creatinine clearance ≥ 30 mL/min (estimated by Cockcroft-Gault equation) 9) Ability to take oral medications and willing to record daily adherence to investigational product.

You may not qualify if:

• Patients with resectable or borderline resectable pancreatic cancer.
• Known history or positive viral test for human immunodeficiency virus (HIV).
• Peripheral sensory neuropathy. 4 )Proven complete dihydropyrimidine dehydrogenase (DPD) deficiency for patients that will be treated with mFOLFIRINOX.
• \) Poor nutritional status (albumin \<3 g/L or weight loss \>10% during the last 4 weeks).
• \) Patients with known active hepatitis (i.e., Hepatitis B or C)
• Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible
• Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA 7) Female: currently pregnant or breast-feeding or who plan to breastfeed while on study though 7 additional days after the last dose of sotorasib and for at least 6 months afterwards after the last dose of gem/nab-P or 15 months after the last dose of mFOLFIRINOX.
• \) Myocardial infarction within 6 months of study Day 1, symptomatic congestive heart failure (New York Heart Association \> class II), unstable angina, or cardiac arrhythmia requiring medication 9) Prior anti-tumor treatment for metastatic or locally advanced pancreatic adenocarcinoma\*. Prior chemotherapy or radiotherapy in the adjuvant or neoadjuvant setting is acceptable if received \> 6 months prior to study enrolment
• \*If initiation of treatment is deemed urgent by the investigator, patients can receive 1st month of Standard of Care (SoC) gem/nab-P (1 cycle) or FOLFIRINOX (2 cycles) during screening. This first month of gem/nab-P or FOLFIRINOX is not a requirement of the study and is not part of this clinical study 10) Active infection requiring antibiotics within 1 weeks of study enrollment. 11) Other malignancy unless curatively treated with no evidence of disease for ≥2 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, and/or ductal carcinoma in situ.
• \) Significant gastrointestinal disorder that results in significant malabsorption, requirement for IV alimentation, or inability to take oral medication.
• \) History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis.
• \) Presence of any condition that, in the opinion of the investigator, renders the patient at high risk from treatment complications or might affect the interpretation of the results of the study.
• \) Significant uncontrolled concomitant disease that could affect compliance with protocol procedures or interpretation of results or that pose a risk to patient safety, in the opinion of the investigator.
• \) Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures at a frequency greater than monthly. Patients with PleurX catheters or intraperitoneal drainage catheters in place may be considered for the study with Medical Monitor approval.
• \) Major surgery within 4 weeks of study Day 1 18) Prior/concomitant therapy:

Sponsors & Collaborators

• GERCOR - Multidisciplinary Oncology Cooperative Group: collaborator
• Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD): lead
• Apices Soluciones S.L.: collaborator

Study Sites (26)

Sainte Catherine - Institut Avignon Provence

Avignon, France, France

NOT YET RECRUITING

Chu Besançon - Hôpital Jean Minjoz

Besançon, France, France

NOT YET RECRUITING

Chu Brest - Hôpital Morvan

Brest, France, France

NOT YET RECRUITING

Chu de Lille - Claude Huriez

Lille, France, France

NOT YET RECRUITING

Hôpital Léon Berard

Lyon, France, France

NOT YET RECRUITING

Chu Bordeaux - Hôpital Haut Lévêque

Pessac, France, France

NOT YET RECRUITING

Chu Poitiers

Poitiers, France, France

NOT YET RECRUITING

Chu Reims - Hôpital Robert Debré

Reims, France, France

NOT YET RECRUITING

Chu Toulouse

Toulouse, France, France

NOT YET RECRUITING

Hôpital Paul-Brousse

Villejuif, France, France

NOT YET RECRUITING

Hospital Universitario Miguel Servet

Zaragoza, Aragon, Spain

RECRUITING

Hospital Clínic

Barcelona, Barcelona, Spain

RECRUITING

Hospital Universitari Vall D'Hebron

Barcelona, Barcelona, Spain

RECRUITING

Institut Català D'Oncologia L'Hospitalet (Ico)

Barcelona, Barcelona, Spain

RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, Spain

RECRUITING

Hospital Reina Sofía

Córdoba, Córdoba, Spain

RECRUITING

Hospital Universitario Donostia-Donostia Unibertsitate Ospitalea

Donostia / San Sebastian, Guipúzcoa, Spain

RECRUITING

Hospital Clínico San Carlos

Madrid, Madrid, Spain

RECRUITING

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Madrid, Spain

RECRUITING

Complejo Hospitalario Regional de Málaga

Málaga, Málaga, Spain

RECRUITING

Complejo Hospitalario de Navarra

Pamplona, Navarre, Spain

RECRUITING

Complexo Hospitalario Universitario de Ourense

Ourense, OURENSE, Spain

RECRUITING

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, Spain

RECRUITING

Hospital Universitario de Salamanca

Salamanca, SALAMANCA, Spain

RECRUITING

Hospital General Universitario de Valencia

Valencia, Valencia, Spain

RECRUITING

MeSH Terms

Interventions

sotorasib

Central Study Contacts

Grupo de Tratamiento de los Tumores Digestivos

CONTACT

+034 913 788 275; secretariattd@ttdgroup.org

Study Design

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

Study Record Dates

• First Submitted: February 5, 2025
• First Posted: March 24, 2025
• Study Start: August 8, 2025
• Primary Completion (Estimated): August 8, 2030
• Study Completion (Estimated): August 8, 2030
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

ES (16); FR (10)