ACT-TIL and ANV419 for Advanced Melanoma.

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05869539

Studienbeginn:
Juni 2023

Letztes Update:
21.07.2023

Wirkstoff:
Combination of Tumor-infiltrating lymphocyte transfer with ANV419

Indikation (Clinical Trials):
Melanoma

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
University Hospital, Basel, Switzerland

Collaborator:
Anaveon AG

Studienleiter

Heinz Läubli, Prof.
Principal Investigator
University Hospital, Basel, Switzerland

Kontakt

Heinz Läubli, Prof.
Kontakt:
Phone: +41 61 265 5074
E-Mail: heinz.laeubli@usb.ch» Kontaktdaten anzeigen

David König, Dr. med.
Kontakt:
Phone: +41 61 265 5074
E-Mail: david.koenig@usb.ch» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

University Hospital Basel
4031 Basel
SwitzerlandRekrutierend» Google-Maps
Ansprechpartner:
Heinz Läubli, Prof.
Phone: +41 61 265 50 74
E-Mail: heinz.laeubli@usb.ch

David König, Dr. med.
Phone: +41 61 265 50 74
E-Mail: david.koenig@usb.ch» Ansprechpartner anzeigen

Studien-Informationen

Detailed Description:

In brief, this trial consists of four study periods: screening, pre-treatment, treatment, and

observational follow-up.

In the screening period, patients are screened for trial eligibility. In the pre-treatment

period, patients have excisional biopsy/surgical resection of tumor lesion(s) (tumor

collection) and TILs are expanded from this lesion/these lesions (TIL expansion). Patients

are permitted to receive bridging therapy outside of the study protocol.

In the treatment period, patients have TIL-ACT. TIL-ACT includes a detailed procedure of

preparative chemotherapy, followed by transfer of the TIL product, followed by in-vivo TIL

expansion with ANV419 (2 doses). TIL transfer is defined as day 0 in the study protocol.

Patients have an End of Treatment visit (14 days after the last study treatment), a safety

follow-up (30 days after the last study treatment) and an efficacy follow up, which is the

End of Study visit (day +90).

Thereafter, patients will transfer to observational follow-up, which is conducted every 3

months until 1 year after TIL transfer.

Patients who terminate the study prematurely during any of the treatment period due to e.g.,

disease progression, toxicity, patient wish, etc. will also transfer to observational

follow-up.

The regimen (TIL-ACT with ANV419) has not been tested. Review by the IDSMB (independent data

safety monitoring board) will be performed after 3 patients (safety check).

Ein-/Ausschlusskriterien

Inclusion Criteria:

Patients who meet all the following criteria will be eligible to participate in the study:

- Must provide written informed consent for the study.

- Must be able to comply with the study protocol as judged by the investigator.

- Are ≥ 18 years. 4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.

- Have pathologically confirmed stage III (unresectable) or stage IV (metastatic)

cutaneous melanoma, as per the American Joint Committee on Cancer staging system, 8th

edition, and have experienced disease progression and exhausted all approved treatment

option with curative intent.

- Have received at least one prior systemic treatment line of PD-(L)1 inhibitor and

BRAF/MEK inhibition in case of BRAFV600 mutated melanoma. Adjuvant systemic treatment

terminated ≥12 months prior to diagnosis of metastatic disease is not counted as a

treatment line.

- Accessible tumor lesion(s) for TIL collection and willingness of the patient to

undergo biopsy/resection of tumor lesion(s).

- Measurable disease as per RECIST v1.1 (following biopsy/resection of tumor lesion(s)

for TIL collection).

- Adequate organ function (pulmonary, cardiovascular, hematological, hepatic, and renal

function) per investigator's judgment. Cardiac stress testing is mandatory for all

patients with underlying cardiac conditions and patients with age ≥50 years. 10.

Female patients of childbearing potential must have a negative serum pregnancy test at

the screening visit and a negative serum pregnancy test within 72 hours prior to start

of preparative chemotherapy (day -7 in the study protocol).

- Female patients who are not postmenopausal, and who have not undergone surgical

sterilization, must agree to use highly effective methods of contraception during the

entire study period and for 6 months after the last dose of study drug. They must also

agree not to donate eggs (ova, oocytes) during the same timeframe.

- Male patients with partners of childbearing potential must agree to use highly

effective methods of contraception and barrier contraception (condom) during the

entire study period and for 6 months after the last dose of study drug. They must also

agree not to donate sperm during the same timeframe.

Exclusion Criteria:

- LDH (lactate dehydrogenase) ≥ 2x upper limit of normal (ULN).

- Life-expectancy ≤ 3 months per investigator's judgment.

- Have not recovered (i.e., ≤ Grade 1 or at baseline with the exception of alopecia or

fatigue [up to Grade 2 allowed]) from immune-related adverse events (irAEs) resulting

from prior immunotherapies. Patients who have endocrine immune-related AEs controlled

by replacement therapy (i.e., hypothyroidism) due to previous treatment are eligible

provided replacement therapy has been initiated and toxicity has returned to Grade 1.

- Have not recovered (i.e., ≤ Grade 1 or at baseline) from toxicities due to a

previously administered chemotherapy, targeted small molecule therapy, or radiation

therapy.

Note: If the patient received major surgery, they must have recovered adequately from the

toxicity and/or complications from the intervention prior to starting study drug. Major

surgery is defined as any surgery requiring entrance into a body cavity (e.g., chest,

abdomen, or brain), organ removal, normal anatomy alteration, or joint replacement. Minor

surgery is defined as any surgery in which skin, mucosa, or connective tissue sections are

altered (e.g., biopsy, cataract, endoscopic procedures, etc.).

- Have been diagnosed with uveal/ocular or mucosal melanoma.

- Have a known additional malignancy (including all in-situ carcinoma) that is

progressing or required active treatment within 2 years prior to enrollment.

Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the

skin that have undergone potentially curative therapy and have no evidence of disease

or in situ cervical cancer in patients who completed cancer-directed therapy or have

evidence of stable disease and do not require active treatment.

- Have active central nervous system metastases and/or carcinomatous meningitis

regardless of clinical stability. Patients with previously treated brain metastases

may participate provided they are stable (without evidence of progression by imaging

for at least 4 weeks prior to study treatment (day -7 in the study protocol), and any

neurologic symptom has returned to baseline. New or enlarging brain metastases, as

well as the use of steroids (≥10 mg of prednisone daily or equivalent) within the last

7 days prior to study drug are excluded.

- Have a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any

other form of immunosuppressive therapy within 7 days prior to study treatment (day -7

in the study protocol).

- Are receiving systemic steroid ≥10 mg of prednisone daily or equivalent for any

reason. Local steroid therapies (e.g., otic, ophthalmic, intra-articular, or inhaled

medications) are acceptable. -

- Have an active autoimmune disease that has required systemic treatment in the past 2

years (i.e., with use of disease modifying agents, corticosteroids, or

immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or

physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency,

etc.) is not considered a form of systemic treatment. 11. Have a known history of, or

any evidence of active, non-infectious pneumonitis.

- Have an active (measurable) and uncontrolled (unresponsive to current therapy)

infectious disease (bacterial, fungal, viral, protozoic).

- Have a history of an acute coronary event (e.g., myocardial infarction) within 3

months prior to study treatment (day -7 in the study protocol), uncontrolled and

symptomatic coronary artery disease, or congestive heart failure New York Heart

Association Class III/IV.

- Have an average QTc interval > 470 msec at ECG-screening.

- Have a history or current evidence of any condition, therapy, or laboratory

abnormality that might confound the results of the study, interfere with the patient's

participation for the full duration of the study, or it is not in the best interest of

the patient to participate, in the opinion of the treating investigator.

- Have known psychiatric or substance abuse disorders that would interfere with

cooperation with the requirements of the study.

- Are pregnant or breastfeeding or expecting to conceive or father children within the

projected duration of the study, starting with the Screening Visit through 6 months

after the last dose of study drug.

- Are known to be human immunodeficiency virus (HIV) positive (or tests positive for HIV

1 or 2 at Screening), unless the following criteria are met:

1. Cluster of differentiation (CD)4+ lymphocyte count > 350 μL.

2. Had no history of acquired immunodeficiency syndrome (AIDS)-defining

opportunistic infections within the past 12 months.

3. Have been on established anti-retroviral therapy for at least 4 weeks.

4. Have an HIV viral load of > 400 copies/mL prior to study treatment (day -7 in the

study protocol).

Note: Patients on strong cytochrome P450 (CYP)3A4 inhibitors or strong CYP3A4 inducers must

be switched to an alternate effective anti-retroviral therapy regimen prior to study

treatment or are excluded if regimen prior to study treatment cannot be altered.

- Have uncontrolled hepatitis B infection or hepatitis C infection. Note: Patients with

hepatitis B (positive hepatitis B surface antigen) who have controlled infection

(serum hepatitis B virus DNA by polymerase chain reaction that is below the limit of

detection and receiving anti-viral therapy for hepatitis B) are permitted. Patients

with controlled infections must undergo periodic monitoring of hepatitis B virus DNA.

Note: Patients with hepatitis C (positive hepatitis C virus antibody) who have

controlled infection (undetectable hepatitis C virus RNA by polymerase chain reaction

either spontaneously or in response to a successful prior course of anti-hepatitis C

virus therapy) are permitted.

- Have received a live vaccine within 30 days of study treatment (day -7 in the study

protocol). Note: Seasonal influenza vaccines for injection are generally inactivated

flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®)

are live attenuated vaccines, and are not allowed.

- Are positive for SARS-CoV2.

- Known hypersensitivity to any of the study therapies or drugs used for TIL production.

- Any other conditions/diseases, dysfunctions, and/or findings, that would

contraindicate the use of any of the study interventions or therapies.

Studien-Rationale

Primary outcome:

1. Incidence of adverse events (%) (Time Frame - up to one year after TIL transfer):
Incidence of adverse events (%) will be recorded to assess safety of combination of Tumor-infiltrating lymphocytes with ANV419

2. Frequency of adverse events (number) (Time Frame - up to one year after TIL transfer):
Frequency of adverse events (number) will be recorded to assess safety of combination of Tumor-infiltrating lymphocytes with ANV419

3. Severity of adverse events (CTCAE v5.0 criteria) (Time Frame - up to one year after TIL transfer):
Severity of adverse events (CTCAE v5.0 criteria) will be recorded to assess safety of combination of Tumor-infiltrating lymphocytes with ANV419. CTCAE (Common Terminology Criteria for Adverse Events): Grade 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal.

Secondary outcome:

1. Objective Response Rate (ORR) (Time Frame - up to one year after TIL transfer):
ORR is defined as the proportion of patients with a best overall response of partial response or better (assessed by the local investigators)

2. Duration of response (DOR) (Time Frame - up to one year after TIL transfer):
DOR is defined as the time from the first documented response and the date of the first documented tumor progression, death, or the last tumor assessment that occurred before subsequent therapy. DOR time for responders who have not progressed or died will be censored at the time of last tumor assessment

3. Progression-fee Survival (PFS) (Time Frame - up to one year after TIL transfer):
The progression-free survival (PFS) is defined as the time from registration to objective tumor progression (determined by local investigators), or death due to any cause, whichever occurred first. PFS time for patients who have not progressed or died will be censored at the time of the last tumor assessment

4. Overall survival (OS) (Time Frame - up to one year after TIL transfer):
OS is defined as the time from registration to the date of death due to any cause

Geprüfte Regime

Combination of Tumor-infiltrating lymphocyte transfer with ANV419:
The study uses a personalized IMP (investigational medicinal product), i.e. TIL product in combination with ANV419. Day 0: Autologous TIL: (minimum 5 x 10^9 and up to 2x 10^11 lymphocytes) administered intravenously over 20 to 30 minutes. Day 0: Intravenous treatment with ANV419 at 243 μg/kg 2 hours after the TIL infusion. Actual body weight will be used to calculate the dose of ANV419. Day14: Intravenous treatment with ANV419 at 243 μg/kg. Actual body weight will be used to calculate the dose of ANV419.

Quelle: ClinicalTrials.gov

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