A Study of LSTA1 When Added to Standard of Care Versus Standard of Care Alone in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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The goal of this clinical trial is to test a new drug plus standard treatment compared with standard treatment alone in patients with advanced head and neck squamous cell carcinoma and cholangiocarcinoma. The main questions it aims to answer are: is the new drug plus standard treatment safe and tolerable is the new drug plus standard treatment more effective than standard treatment

Detailed Description
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This is a Phase 2a, double-blind, placebo-controlled, multi-center, randomized study of LSTA1 when added to standard of care (SoC) versus SoC alone in patients with advanced solid tumors. The study will include patients with advanced head and neck squamous cell carcinoma (HNSCC) and cholangiocarcinoma. The study will consist of a screening period, a run-in period, a treatment period, an end-of-treatment follow-up visit, and a long-term follow up period. Participants who provide informed consent will be screened for eligibility within 28 days prior to beginning the study treatment run-in period. Once eligibility is confirmed, participants will be randomized to one of the two treatment groups (SoC + placebo vs. SoC + LSTA1). During the 3-day run-in period, participants will only receive the LSTA1 or placebo components of their randomized treatment regimen. After the 3-day run-in, Cycle 1 of treatment will commence. Tumor scans will be performed every 8 weeks (56 days ± 7 days) while on treatment.

Official Title
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A Phase 2a, Double-blind, Placebo-controlled, Multi-center, Randomized Study Evaluating LSTA1 When Added to Standard of Care (SoC) Versus Standard of Care Alone in Subjects With Advanced Solid Tumors

Conditions
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Cholangiocarcinoma, Head and Neck Squamous Cell Carcinoma, Advanced Head and Neck Squamous Cell Carcinoma, Head and Neck Cancer, Gallbladder Cancer, Gallbladder Carcinoma, Intrahepatic Cholangiocarcinoma, Extrahepatic Cholangiocarcinoma, Bile Duct Cancer, Cancer of the Head and Neck, HNSCC, Oropharynx Cancer, Oral Cavity Cancer, Hypopharynx Cancer, Larynx Cancer, Oral Cavity Squamous Cell Carcinoma, Squamous Cell Carcinoma of Head and Neck, Squamous Cell Carcinoma of the Head and Neck, Squamous Cell Carcinoma of the Larynx, Squamous Cell Carcinoma of the Hypopharynx, Squamous Cell Carcinoma of the Oral Cavity, Squamous Cell Carcinoma of the Oropharynx, Gall Bladder Cancer, Gall Bladder Carcinoma, Oropharynx Squamous Cell Carcinoma, Hypopharynx Squamous Cell Carcinoma, Larynx Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: LSTA1
* Drug: Paclitaxel
* Drug: Durvalumab
* Drug: Cisplatin
* Drug: Gemcitabine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Life expectancy ≥ 3 months At least one measurable metastatic lesion as assessed by RECIST 1.1 Adequate organ and marrow function Adequate contraception Patients with any of the following: Histologically confirmed recurrent or metastatic HNSCC that is unresectable or considered incurable by local therapies and that has progressed after first-line immunotherapy. The eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. Patients may not have primary tumor sites of the skin, paranasal sinuses, or the nasopharynx (any histology). Pathologically confirmed metastatic or unresectable cholangiocarcinoma or gallbladder carcinoma (GBC), with no prior systemic chemotherapy or targeted therapy or loco-regional therapy (including but not limited to transarterial chemoembolization, transarterial embolization, transarterial chemotherapy or transarterial radioembolization). Patients with recurrent disease more than 6 months after completion of adjuvant chemotherapy following curative resection are eligible. Exclusion Criteria: Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results, including but not limited to: Any major surgery or irradiation less than 4 weeks prior to baseline disease assessment Active infection (viral, fungal, or bacterial) requiring systemic therapy Known active hepatitis B virus, hepatitis C virus, or HIV infection Active tuberculosis as defined per local guidance History of allogeneic tissue/solid organ transplant Prior malignancy requiring active treatment within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast Pregnant or breastfeeding Clinically significant or symptomatic cardiovascular/cerebrovascular disease (incl. myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) within 6 months before randomization History or clinical evidence of symptomatic central nervous system (CNS) metastases Has known allergies to taxanes or their standard pretreatments for unresectable or metastatic HNSCC For cholangiocarcinoma, active autoimmune disease that might deteriorate when receiving an immune-stimulatory agent. Patients with Type 1 diabetes, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LSTA1 arm for Advanced Head and Neck Squamous Cell Carcinoma<br> | Drug: LSTA1<br>* LSTA1 3.2 mg/kg given as a slow IV push over 1 minute when standard treatment(s) are given<br>Drug: Paclitaxel<br>* paclitaxel 175 mg/m^2 IV administered over 3 hours every 21 days<br>|
| Experimental: LSTA1 arm for Cholangiocarcinoma<br> | Drug: LSTA1<br>* LSTA1 3.2 mg/kg given as a slow IV push over 1 minute when standard treatment(s) are given<br>Drug: Durvalumab<br>* 1500 mg of durvalumab IV administered over 1 hour every 21 days for 8 cycles then every 28 days for additional cycles<br>Drug: Cisplatin<br>* cisplatin 25 mg/m^2 IV administered over 30 minutes on day 1 and day 8 every 21 days for up to 8 cycles<br>Drug: Gemcitabine<br>* gemcitabine 1000 mg/m^2 IV administered over 30 minutes on day 1 and day 8 every 21 days up to 8 cycles<br>|
| Placebo Comparator: Placebo arm for Advanced Head and Neck Squamous Cell Carcinoma<br> | Drug: Paclitaxel<br>* paclitaxel 175 mg/m^2 IV administered over 3 hours every 21 days<br>Drug: Placebo<br>* Placebo given as a slow IV push over 1 minute when standard treatment(s) are given<br>|
| Placebo Comparator: Placebo arm for Cholangiocarcinoma<br> | Drug: Durvalumab<br>* 1500 mg of durvalumab IV administered over 1 hour every 21 days for 8 cycles then every 28 days for additional cycles<br>Drug: Cisplatin<br>* cisplatin 25 mg/m^2 IV administered over 30 minutes on day 1 and day 8 every 21 days for up to 8 cycles<br>Drug: Gemcitabine<br>* gemcitabine 1000 mg/m^2 IV administered over 30 minutes on day 1 and day 8 every 21 days up to 8 cycles<br>Drug: Placebo<br>* Placebo given as a slow IV push over 1 minute when standard treatment(s) are given<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | The National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE) will be used to grade the intensity of adverse events throughout the study | 30 days after treatment discontinuation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunotherapy, chemo, chemotherapy