A Phase 1/1b First-in-human Dose Escalation and Expansion Study for the Evaluation of Safety, Pharmacokinetics, Pharmacodynamics, and Anti-tumor Activity of SAR439459 Administered Intravenously as Monotherapy and in Combination with cemiplimab in Adult Patients with Advanced Solid Tumors
- Conditions
- 10027655Advanced solid tumors
- Registration Number
- NL-OMON55468
- Lead Sponsor
- Genzyme Europe BV
- Brief Summary
Trial ended prematurely
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 12
Dose escalation (Part 1A and Part 1B):, -Patients with histologically
confirmed, advanced unresectable or metastatic solid tumor whom in the opinion
of the Investigator does not have a suitable alternative therapy.,
Dose expansion (Part 2A):, -Patients with histologically confirmed, advanced
unresectable melanoma whom in the opinion of the Investigator does not have a
suitable alternative therapy
-Patients must have failed any prior therapy based on anti-PD-1 or anti-PD-L1
as defined by disease progression within 26 weeks of initiating anti-PD-1 or
anti-PDL-1-based therapy without any evidence of a response.
-Patients must have a site of disease amenable to biopsy and be a candidate for
tumor biopsy.
-Patients must be able and willing to provide mandatory tumor biopsies prior to
and during study treatment.,
Dose expansion (Part 2B):, -Patients with avanced unresectable or metastatic
melanoma who failed after one prior therapy based on anti-PD-1 or anti-PD-L1 or
colorectal adenocarcinoma with mesenchymal molecular subtype or urothelial
cancer and have failed platinum-containing chemotherapy or non-small cell lung
cancer (NSCLC) after failure of anti-PD-1 or anti PD-L1, or hepatocellular
carcinoma (HCC) after failure of anti-PD-1 or anti PD-L1, with or without
bevacizumab.
For all indications patients must not have a suitable alternative approved
standard therapy available in the opinion of the investigator or must be
refused by the patient., Dose expansion parts 2A and 2B:, -At least 1
measurable lesion by RECIST v1.1.
-Age < 18 years.
-Eastern Cooperative Oncology Group (ECOG) performance status >1.
-Concurrent treatment with any other anticancer therapy (including radiotherapy
or investigational agents) or participation in another clinical study.
-Washout period of less than 3 weeks to prior anticancer therapy.
-Significant and uncontrolled concomitant illness, including any psychiatric
condition.
-Active infections, including unexplained fever (temperature >38.1ºC), or
antibiotic therapy within 1 week prior to enrollment.
-Any prior organ transplant including allogeneic bone marrow transplant.
-History within the last 5 years of an invasive malignancy other than the one
treated in this study.
-History of known HIV, unresolved viral hepatitis.
-Any major surgery within the last 28 days.
-Patients with primary central nervous system (CNS) tumors and/or CNS
metastases of non-CNS primary tumors that are untreated.
-History of severe, acute or chronic heart diseases.
-History of severe, acute or chronic renal diseases or inadequate renal
function.
-History of significant valvular heart disease (including valve replacement),
vascular malformation and anurysm
-Any of the following within 6 months prior to study enrollment: pulmonary
embolism, deep vein thrombosis, active uncontrolled bleeding, infectious or
inflammatory bowel disease, diverticulitis, intestinal obstruction or
perforation and gastrointestinal hemorrhage.
-Inadequate hematological, renal or liver function.
-Non-resolution of any prior treatment related toxicity to Grade <2.
-Prior treatment with any anti-TGF-β inhibitors.
-Known allergies to any component of SAR439459 and/or REGN2810.
-Patients with uveal melanoma and patients with prior or ongoing uveitis.
-Patients who received prior immunotherapy who developed toxicity leading to a
permanent discontinuation of immunotherapy.
-Ongoing or recent (within 2 years) evidence of significant autoimmune disease
that required treatment with systemic immunosuppressive treatments.
-Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent)
within 4 weeks prior to the first dose of SAR439459 and/or REGN2810 (occasional
use of inhaled, intraocular, nasal or topical steroids for symptomatic relief
allowed).
-History of pneumonitis or bowel perforation.
-Patients with underlying cancer predisposition syndromes.
-Therapeutic doses of anticoagulants or antiplatelet agents within 7 days prior
the first dose of SAR439459
-Receipt of a live vaccine within 30 days of planned start of study medication.
-Prothrombin time (PT) or international normalized ratio (INR) > 1.5 × ULN
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- Incidence of DLTs at Cycle 1 and 2 (Day 1 to Day 28) in Parts 1A and 1B.<br /><br><br /><br>- Objective Response Rate (ORR) for Part 2B: Efficacy as documented by ORR will<br /><br>be assessed by evaluation of anti-tumor response information according to<br /><br>RECIST 1.1 (Part 2A and 2B).</p><br>
- Secondary Outcome Measures
Name Time Method