LSTA1 Phase 2a basket trial in advanced solid tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Lisata Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

completed 15 Mar 2024

Decision date (initial)

2023-08-14

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Lisata Therapeutics, Inc.

External identifiers

EU CT number

2023-503740-14-00

WHO UTN

U1111-1291-8700

ClinicalTrials.gov

NCT05712356

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacodynamic, Therapy, Pharmacokinetic

To evaluate the safety of LSTA1 in combination with SoC therapies compared to SoC therapies alone

Secondary objectives 1

1. To determine the therapeutic effect of LSTA1 when added to SoC in patients with advanced solid tumors on: • Overall survival (OS) • 12-month survival • Progression-free survival (PFS) • Duration of response (DOR) in responding patients with measurable disease at baseline − Objective response rate (ORR) − Duration of response (DOR) To evaluate the safety profile of LSTA1 when administered as monotherapy during the run-in period To evaluate the dose tolerance of SoC therapy when administered along with LSTA1

Conditions and MedDRA coding

Head and neck cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. Subjects must be ≥ 18 years of age at time of consent and provide informed consent
2. 11. Inclusion Criteria First-line Cholangiocarcinoma - 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 a) Includes intrahepatic cholangiocarcinoma (IHC), extrahepatic cholangiocarcinoma (EHC), and gallbladder carcinoma (GBC), but not ampulla of Vater cancers b) For liver dominant IHC, disease must comprise < 60% of the liver parenchyma, as defined by computed tomography (CT) liver segmental volumetrics
3. 12. If the patient has had decompression of the biliary tree within the last 14 days, stability of the bilirubin level needs to be confirmed with two measurements that are within 5 to 7 days of each other; (the second measurement must be obtained within 7 days prior to randomization); both the first and second measurement must be ≤ 1.5 x ULN; stability is defined as the second measurement being no more than one point higher than the first
4. 2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
5. 3. Life expectancy ≥ 3 months, as determined by the investigator
6. 4. At least one bidimensional measurable metastatic lesion assessed by RECIST 1.1. Tumor lesion located in the area of previous radiotherapy or other local and regional treatment sites is generally not a measurable lesion unless there is definite progression of the lesion, or the lesion persists three months after radiotherapy. Additionally, a biopsy site should not be considered a target lesion.
7. 5. Adequate organ and marrow function: • Platelets ≥ 100 x 109/L (>100,000 per mm3) • WBC ≥ 3000/μL • Absolute neutrophil count ≥ 1.5 x 109/L • Serum albumin ≥ 2.5 g/L • ALT and AST ≤ 2.5 x ULN in the absence of liver metastases or < 5 x ULN in the presence of liver metastases • Bilirubin ≤ 1.5 x ULN • Hemoglobin ≥ 9.0 g/dL. Labs may be drawn 24 hours after a transfusion to meet this criterion. • INR < 1.5 (for patients not receiving therapeutic anticoagulation) • Adequate respiratory and cardiac function (PaO2 ≥ 60 mm Hg or oxygen saturation ≥ 92% on room air, and 12-lead ECG with normal tracing or non clinically significant changes that do not require medical intervention) • QT interval corrected using the Fridericia method (QTcF) < 470 ms
8. 6. Adequate contraception: • All female patients will be considered to be of childbearing potential unless they are postmenopausal (at least 12 months consecutive amenorrhea, in the appropriate age group and without other known or suspected cause) or have been sterilized surgically. Female patients of childbearing potential must agree to use two forms of highly effective contraception methods (a primary and a secondary method – see next bullet) during the study and for a period of 6 months following the last administration of the study drug, unless subject received cisplatin whereby aforementioned contraception methods must be adhered to for 14 months. • Male patients and their female partners, who are of childbearing potential and are not practicing total abstinence, must agree to use two forms of highly effective contraception methods (a primary and a secondary method) during the study and for a period of 6 months following the last administration of the study drug, unless subject received cisplatin whereby the following contraception methods must be adhered to for 14 months. These contraception methods include oral, transdermal, systemic or implant contraception birth control, intra-uterine devices (IUD), abstinence and double barrier method such as diaphragm with spermicidal gel or other recommended double barrier methods screening.
9. 7. Inclusion Criteria Second-line Head and Neck Squamous Cell Carcinoma (HNSCC) - Patients with histologically confirmed recurrent or metastatic HNSCC that is unresectable or considered incurable by local therapies and that has progressed after first-line immunotherapy • Characterization of tumor PD-L1 expression using the PD-L1 IHC 22C3 PharmDx Assay • Receipt of prior treatment with checkpoint inhibitors as a single agent and have received at least 2 doses of the agent or a minimum of 6 weeks on treatment • Have documented clinical or radiographic progression by RECIST 1.1
10. 8. 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).

Exclusion criteria 23

1. 1. 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 HBV, HCV, 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 • 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; Pregnant or breastfeeding
2. 19. Concurrent use of immunosuppressive medication, EXCEPT for the following: a. Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection) b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
3. 2. Subjects with a known sensitivity to LSTA1 or its excipients
4. 20. 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. Active or prior documented inflammatory bowel disease (e.g., Crohn’s disease or ulcerative colitis)
5. 21.Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab. Note: While enrolled, patients should not receive any live vaccines while receiving durvalumab and up to 30 days after last dose of durvalumab.
6. 22.Patients who experience any grade 3-4 gastrointestinal (GI) bleeding within 3 months preceding randomization
7. 23.Diagnosis of sclerosing cholangitis
8. 24.Diagnosis of hepatic encephalopathy
9. 25.Current biliary obstruction requiring surgical diversion or placement of endoscopic or transhepatic stents for biliary decompression
10. 26.Clinically significant ascites (palpable on exam, paracentesis in last 3 months preceding randomization, and/or symptomatic)
11. 27.History of malignant bowel obstruction
12. 10. Creatinine clearance < 45 mL/min (calculated using the Cockcroft-Gault formula below:) • Female CrCl = (140 - age in years) x weight in kg x 0.85 / 72 x serum creatinine in mg/dL • Male CrCl = (140 - age in years) x weight in kg x 1.00 / 72 x serum creatinine in mg/dL
13. 28.Subjects with creatinine clearance < 60 mL/min (calculated using the Cockcroft-Gault formula below:) • Female CrCl = (140 - age in years) x weight in kg x 0.85 / 72 x serum creatinine in mg/dL • Male CrCl = (140 - age in years) x weight in kg x 1.00 / 72 x serum creatinine in mg/dL
14. 3. Patients with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent
15. 4. Have received chemotherapy, radiotherapy, biotherapy, endocrine therapy, immunotherapy, and other anti-tumor therapy within 28 days prior to randomization
16. 5. History or clinical evidence of CNS metastases; exceptions include: • Subjects who have completed local therapy and who meet both of the following criteria: − Subjects must be asymptomatic AND − Subjects must have no requirement for steroids 6 weeks prior to start of study treatment. Screening with CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS Metastases
17. UPD 6. Exclusion Criteria Second-line Head and Neck Squamous Cell Carcinoma (HNSCC) - Patients who received prior taxanes unless it was given as part of neoadjuvant, concurrent therapy in the curative intent setting and it has been more than 6 months since last dose
18. 7. Known allergies to taxanes or their standard pretreatments
19. 8. Any surgery involving the HNSCC for which the patient is being treated (except biopsies) that occurred within 28 days prior to randomization
20. UPD 9. Subjects who cannot discontinue any concomitant medications that are inducers or inhibitors of CYP2C8 (e.g., rifampicin, phenobarbital, secobarbital, phenytoin, clopidogrel, gemfibrozil, zafirlukast, felodipine) ) or CYP3A4 (e.g., dexamethasone, carbamazepine, phenytoin, phenobarbital, rifampin/rifampicin, rifabutin, St. John’s Wort, erythromycin, itraconazole, ritonavir, verapamil) during treatment with paclitaxel
21. 16. Exclusion Criteria First-line Cholangiocarcinoma - Patients who received prior palliative systemic treatment for their advanced cancer
22. 17. Patients with a history of idiopathic pulmonary fibrosis (pneumonitis requiring treatment with steroids), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on baseline imaging
23. 18. Patients with a history of active interstitial lung disease

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence and severity of adverse events

Secondary endpoints 4

1. overall survival
2. progression free survival
3. Objective response rate
4. Duration of response

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Lisata Therapeutics Inc.

Sponsor organisation

Lisata Therapeutics Inc.

Address

110 Allen Road Fl 2

City

Basking Ridge

Postcode

07920-4500

Country

United States

Scientific contact point

Organisation

Lisata Therapeutics Inc.

Contact name

Dr. Kristen K. Buck, MD

Public contact point

Organisation

Lisata Therapeutics Inc.

Contact name

Kathryn Shantz

Third parties 6

Sponsor responsibilities

Article 77 compliance

Lisata Therapeutics Inc.

Contact point sponsor

Lisata Therapeutics Inc.

Article 77 implementation

Lisata Therapeutics Inc.

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications