Tumor treatment with autologous immune cells and ANV419 in patients with advanced melanoma. The BaseTIL-03M study.

Switzerland (ICTRP)

ICTRP Trial ID
NCT05869539 (ICTRP)

Official title (approved by ethics committee)
A Phase I trial of Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and ANV419 in patients with advanced melanoma. The BaseTIL-03M trial (BASEC)

Academic title
A Phase I Trial of Adoptive Cell Therapy With Tumor-Infiltrating Lymphocytes and ANV419 in Patients With Advanced Melanoma. The BaseTIL-03M Trial (ICTRP)

Public title
ACT-TIL and ANV419 for Advanced Melanoma. (ICTRP)

Disease under investigation
Advanced Melanoma (ICTRP)

Intervention under investigation
Drug: Combination of Tumor-infiltrating lymphocyte transfer with ANV419 (ICTRP)

Type of trial
Interventional (ICTRP)

Trial design
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Inclusion/Exclusion criteria
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 L.

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 (d (ICTRP)

not available

Primary and secondary end points
Incidence of adverse events (%);Frequency of adverse events (number);Severity of adverse events (CTCAE v5.0 criteria) (ICTRP)

Objective Response Rate (ORR);Duration of response (DOR);Progression-fee Survival (PFS);Overall survival (OS) (ICTRP)

Registration date
not available

Incorporation of the first participant
not available

Secondary sponsors
Anaveon AG (ICTRP)

Additional contacts
Heinz L?ubli, Prof.;Heinz L?ubli, Prof.;Heinz L?ubli, Prof., heinz.laeubli@usb.ch, +41 61 265 5074;+41 61 265 50 74, University Hospital, Basel, Switzerland, (ICTRP)

Secondary trial IDs
2023-00575, th23laeubli (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT05869539 (ICTRP)