Clinical trial NCT06821503: Clinical Study Evaluating the Safety, Tolerability, and Preliminary Efficacy of LM-108 ± Penpulimab+Chemotherapy in Advanced Solid Tumors - Cohort C
Official title: An Open Label Phase Ib/II Clinical Study Evaluating the Safety, Tolerability, and Preliminary Efficacy of LM-108 ± Penpulimab Plus Chemotherapy in Patients With Advanced Solid Tumors - Cohort C
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Pancreatic Cancer
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-02-12
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is the cohort C part of a multicenter, open label Phase Ib/II clinical study evaluating the preliminary efficacy, safety, and tolerability of LM-108 combined with anti-tumor therapy in patients with advanced solid tumors. The dose of LM-108 combined with penpulimab, albumin paclitaxel, and gemcitabine is recommended in Phase Ib.Explore the efficacy and safety of LM-108 combined with anti-tumor therapy in patients with advanced pancreatic cancer in Phase II.


Eligibility criteria: Inclusion Criteria:

* Age 18 or above.
* The Eastern Cooperative Oncology Group (ECOG) physical fitness status score is 0-1 points.
* There should be at least one measurable lesion.
* All acute toxic reactions caused by previous anti-tumor treatments or surgical procedures have been relieved to grade 0-1 or to the levels specified in the inclusion/exclusion criteria.
* Have sufficient organ and bone marrow function
* Expected survival period ≥ 12 weeks
* Infertility is defined as women who have reached menopause or have undergone bilateral oophorectomy with medical records. Male participants and female participants with fertility must agree to use one medically approved contraceptive measure during the trial period and within 6 months after the last administration of the trial drug or within 9 months after the last administration of chemotherapy drug (oxaliplatin) (whichever is later). The serum pregnancy test must be negative within 3 days before starting the study medication and not during lactation.
* With my consent and signed informed consent form.
* Patients diagnosed with Pancreatic ductal adenocarcinoma (PDAC) by pathology have evidence of advanced stage or metastasis that cannot be surgically removed.
* Have not received systematic treatment for unresectable locally advanced or metastatic PDAC in the past

Exclusion Criteria:

* Known High-frequency microsatellite instability (MSI-H)/deficient mismatch repair (dMMR).
* There is uncontrolled or symptomatic active central nervous system metastasis, which can manifest as clinical symptoms, cerebral edema, spinal cord compression, cancerous meningitis, leptomeningeal disease, and/or progressive growth.
* Within 14 days prior to enrollment, there were still uncontrollable pleural effusion and ascites despite treatment such as puncture and drainage; Pericardial effusion accompanied by clinical symptoms or moderate or above.
* Within 14 days prior to enrollment, there is an unresolved biliary obstruction, or the clinical status has remained stable for less than 14 days after biliary stent implantation.
* Participants' weight has decreased by more than 20% or their body mass index (BMI) is less than 18 kg/m ² within the first 2 months of enrollment.
* Received the following treatments or medications before enrollment:

  1. Prior to enrollment, received treatment with C-C chemokine Receptor 8 (CCR8) antibodies, cytotoxic T-lymphocyte associated protein-4 (CTLA-4) antibodies, or other drugs that act on Tregs.
  2. Having undergone major surgery within 28 days prior to enrollment.
  3. Used immunosuppressive drugs within 14 days prior to enrollment.
  4. Vaccination with attenuated live vaccine should be administered within 28 days prior to enrollment or planned within the study period and 60 days after completion of study drug treatment.
  5. Received anti-tumor therapy (including chemotherapy, radiotherapy, immunotherapy, endocrine therapy, targeted therapy, biological therapy, or tumor embolization) within 28 days before enrollment.
* Diagnosed with any other malignant tumor within the 5 years prior to enrollment.
* There are any active, known or suspected autoimmune diseases present.
* Within the first 3 months of enrollment, there have been significant clinical bleeding symptoms or clear bleeding tendencies; Arterial/venous thrombotic events that occurred within the first 6 months of enrollment.
* Significant vascular disease occurred within the first 6 months of enrollment.
* Severe, unhealed, or cracked wounds, as well as active ulcers or untreated fractures.
* There is peripheral neuropathy of grade\>1 present.
* Have experienced gastrointestinal perforation and/or gastrointestinal fistula within the 6 months prior to enrollment;
* Within the 6 months prior to enrollment, there have been clinical signs or symptoms of intestinal obstruction and/or gastrointestinal obstruction.
* Existence of interstitial lung disease, non infectious pneumonia, or uncontrolled systemic diseases.
* Known to be allergic to the investigational drug or any of its excipients; Or have experienced severe allergic reactions to other monoclonal antibodies.
* Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), untreated active hepatitis or co infection with hepatitis B and hepatitis C.
* Clinical symptoms or diseases of the heart that have not been well controlled:
* Systemic use of antibiotics for at least 7 days within the 28 days prior to enrollment, or unexplained fever\>38.5 °C during screening/before first administration.
* Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
* Have participated in any other drug clinical studies within 4 weeks prior to enrollment, or have not had more than 5 half lives since the last study medication.
* Known history of abuse or drug use of psychotropic substances.
* There are other serious physical or mental illnesses or laboratory abnormalities that may increase the risk of participating in the study, or interfere with the study results, as well as patients who the researcher deems unsuitable to participate in this study.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Baseline up to 28 days
measure: Progression-Free Survival (PFS)
timeFrame: Up to 48 weeks
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Up to 96 weeks
measure: Duration of Response (DOR)
timeFrame: Up to 48 weeks
measure: Overall response rate (ORR)
timeFrame: Up to 48 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: BeiJing
country: China
facility: Cancer Hospital Chinese Academy of Medical Science
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Chongqing
country: China
facility: Chongqing Qeneral Hospital
state: Chongqing
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Huazhong University of Science and Technology Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Provincial People's Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Shenyang
country: China
facility: The First Affiliated Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: The Sixth People's Hospital of Shenyang
state: Liaoning
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University Medical College
state: Shaanxi
city: Shanghai
country: China
facility: The First Affiliated Hospital of Naval Medical University
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Cancer Hospital Airport Hospital
state: Tianjin
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
state: Tianjin
Study officials:
References: