Study Sponsor: Innate Pharma SA

Location: Frauenshuh Cancer Center

Phase of Study: Phase 1

Purpose of study: STELLAR-001: A phase I study of the anti-C5aR, IPH5401, in combination with the anti-PD-L1, durvalumab, in patients with selected advanced solid tumors.

Inclusion Criteria:
Patients must meet all of the inclusion criteria in order to be eligible to participate in the
study.
-Dose escalation: Patients with advanced and/or metastatic histologicallyconfirmed
HCC, UCC, RCC or NSCLC solid tumors with evidence of active
disease, who have been treated with a minimum of one line of systemic therapy in
the metastatic setting. Patients should have received known standard therapies
(including platinum-based chemotherapy in patients with UCC), unless not
available or contraindicated.
-Cohort expansion
i. NSCLC:
a. Histologically confirmed unresectable advanced and/or metastatic NSCLC
b. Patients should have been treated with no more than two lines of systemic
therapies in the advanced/metastatic setting that include platinum based
chemotherapy.
c. Patients should have received anti-PD1/anti-PD-L1 either as:
i. Single agent: In this case, patients should have had either RECIST
response or stable disease for a minimum of 6 months before disease
progression.
ii. In combination with first line platinum-based chemotherapy: In this
case, patients should have had a RECIST response for a minimum of 6
months before disease progression.
ii. HCC:
a. Histologically confirmed unresectable advanced and/or metastatic HCC.
b. Child-Pugh Score Class A.
c. Patients should have been previously treated with no more than 2 lines of
systemic therapy in the advanced/metastatic setting that should include
sorafenib.
d. Patients should be naïve to treatment with anti-PD1/anti-PD-L1 therapy.
-At least 18 years of age.
-ECOG performance status of ≤1.
-Adequate organ function defined as:
a. Hematological
i. Absolute neutrophilic count ≥ 1.5 x 109/L
a. For HCC ≥ 1.0 x 109/L
ii. Hemoglobin ≥ 9.0 g/dL
iii. Platelet count ≥ 75 x 109/L
b. Hepatic
i. Total bilirubin ≤ 1.5 x ULN
a. For HCC ≤ 2 x ULN
ii. AST and ALT ≤ 3 x ULN (and up to 5 x ULN in the presence of liver
metastases)
iii. Albumin ≥ 3.3 g/dL (except for patients with HCC: albumin ≥ 2.8 g/dL)
iv. For HCC: INR < 1.7
c. Renal: calculated creatinine clearance (Cockcroft-Gault formula ≥ 50 mL/min
-At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target
lesion (TL) at baseline.
-Feasibility of obtaining tumor biopsy for patients included in the cohort expansion.
-All AEs while receiving prior treatment with immunotherapy must have completely
resolved or resolved to Grade 1 prior to screening for this study.
-No active viral hepatitis B or C.
a. Active hepatitis B is defined by HBV DNA and/or HBsAg positivity.
b. Active hepatitis C is defined by HCV RNA positivity.
-Women of childbearing potential must have a negative serum or urine beta-HCG
pregnancy test result within seven days of treatment and must practice an effective
method of contraception during treatment and for at least 6 months (180 days)
following the last dose of study drug.
-Male patients who are sexually active with a female partner of childbearing
potential must agree to practice effective barrier contraception during treatment
and for at least 6 months (180 days) following the last dose of study drug.
-Ability to understand and the willingness to sign a written informed consent
document.
-A minimum life expectancy of 3 months.
-Accept to comply with all procedures described in the protocol.

Exclusion Criteria:
Patients meeting any of the following exclusion criteria will not be eligible to participate in the
study:
1) For patients with NSCLC:
a. Known actionable mutation or rearrangement (including but not limited to
epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK)
gene rearrangements, ROS-1 alterations, or BRAF mutations).
2) For patient with Hepatocellular carcinoma:
a. Hepatic encephalopathy in the past 12 months.
b. Ascites that requires repeated paracentesis in the past 2 months.
c. Main portal vein thrombosis.
d. Active or prior history of gastrointestinal bleeding in the past 12 months.
e. Prior hepatic transplantation.
3) Patients with known spinal cord compression.
4) Symptomatic, untreated, or actively progressing central nervous system (CNS)
metastases. Patients with suspected CNS metastases at screening should have
an MRI (preferred) or CT each preferably with IV contrast of the brain prior to
study entry to rule them out. Asymptomatic patients with treated CNS lesions are
eligible, provided that all of the following criteria are met:
– Measurable disease, per RECIST v1.1, must be present outside the CNS.
– The patient has no history of intracranial hemorrhage or spinal cord
hemorrhage.
– The patient has not undergone stereotactic radiotherapy within 7 days prior to
initiation of study treatment, whole-brain radiotherapy within 14 days prior to
initiation of study treatment, or neurosurgical resection within 28 days prior to
initiation of study treatment.
– The patient has no ongoing requirement for corticosteroids as therapy for CNS
disease. Anti-convulsant therapy at a stable dose is permitted.
5) Patients with tumors known to be microsatellite instable (i.e. MSI-High).
6) Prior treatment with systemic therapies that modulate myeloid derived suppressor
cells (MDSCs), including but not restricted to anti-colony stimulating factor 1
(CSF-1).
7) Known allergic reactions attributed to compounds of similar product.
8) Patients with any serious underlying medical condition that would impair the
patient from receiving or tolerating the planned treatment.
9) Concurrent enrollment in another clinical trial, unless it is an observational (non –
interventional) clinical study or the follow-up period of an interventional study.
10) Any concurrent treatment with any anti-cancer therapy including but not restricted
to chemotherapy, hormonal therapy, biological therapy or immunotherapy.
11) Systemic treatment with steroids or other immunosuppressive agents within 14
days prior to entry with the exception of intranasal, inhaled, or topical steroid,
systemic prednisone at doses not exceeding 10 mg/day (or equivalent) or steroids
as premedication for hypersensitivity reaction.
12) Receipt of live attenuated vaccine within 30 days prior to the first dose of study
drug
13) Active auto-immune disease within the past 2 years. Patients with vitiligo,
alopecia, Grave’s disease, hypothyroidism (e.g., following Hashimoto syndrome)
stable on hormone replacement, or psoriasis not requiring systemic treatment
(within the past 3 years) are not excluded
14) History of adverse events that resulted in permanent discontinuation of prior
immunotherapy.
15) ≥ Grade 3 immune-related AE or an immune-related neurologic or ocular AE of
any grade while receiving prior immunotherapy. Patients with endocrine AE of ≤
Grade 2 are permitted to enroll if they are stable on appropriate replacement
therapy and are asymptomatic. Immune-related AE would include dermatological
(e.g. rash, eruptions), gastrointestinal (e.g. colitis, hepatitis, pancreatitis),
endocrine (e.g. hypophysitis, thyroid or adrenal insufficiency), respiratory (e.g.
pneumonitis), ocular (e.g., uveitis, conjunctivitis), neurological (e.g. paresthesia,
myelitis), renal (e.g. renal failure), hematological (e.g. autoimmune cytopenia, red
cell aplasia), or mucosal toxicities (e.g. oral mucositis, dry mouth).
16) Patients who have undergone major surgery <28 days prior to starting study drug.
17) Treatment with any conventional or investigational anticancer therapy within 28
days prior to first study product administration.
18) Primary immunodeficiency and/or history of allogenic bone marrow
transplantation.
19) Current active infection.
20) Positive test results for human immunodeficiency virus.
21) Patients with a history of other active invasive malignancies during the past three
years. Patients with history of other cancer > 3 years prior to enrollment could be
enrolled provided that they are considered cured by their treating physician and
are not receiving any form of “maintenance” therapy.
22) Pregnant or breastfeeding women.
23) Patients with abnormal cardiac history within 6 months before inclusion or with
history of myocardial infarction.
24) Patients with dementia or altered mental status that would preclude
understanding and rendering of informed consent document.

Study Contact:
Amy Feist
(952) 993-6071
Amy.Feist@parknicollet.com