A Phase 1/2, open label, first-in-human, dose escalation and expansion study for the evaluation of safety, pharmacokinetics, pharmacodynamics, and anti-tumor activity of SAR445877 administered as monotherapy in adults with advanced solid tumors
- Conditions
- advanced stage cancer10027655
- Registration Number
- NL-OMON53618
- Lead Sponsor
- Sanofi-aventis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 81
I 01. Participant must be at least 18 years of age inclusive, at the time of
signing the informed consent.
Dose escalation Part 1:
I 02. Participants with advanced unresectable or metastatic solid tumors for
which, in the judgement of the investigator, no standard alternative therapy is
available or is not in the best interest of the participant.
Dose expansion Part 2:
Cancer diagnosis:
I 03. Participants in Cohort A: Histologically or cytologically confirmed
diagnosis of metastatic NSCLC.
I 04. Participants in Cohort B: Histologically or cytologically confirmed
diagnosis of advanced unresectable or metastatic HCC, or clinically by American
Association for the Study of Liver Diseases (AASLD) criteria in cirrhotic
patients (participants without cirrhosis must have had histological
confirmation of diagnosis).
I 05. Participants in Cohort C: Histologically or cytologically confirmed
diagnosis of advanced unresectable or metastatic GC or Siewert Type 2 & 3 GEJ.
I 06. For participants in Cohort C: Disease with CPS scoring of <1 as
determined at local laboratory with an Agency approved test (for the other
cohorts: Disease with any CPS scoring. No need for CPS determination at local
laboratory).
I 07. For participants in Cohort C: Participants must have MSI or MMR status
known or determined locally and must have non-MSI-H or proficient MMR (pMMR)
disease to be eligible.
I 08. For participants in Cohort C: Participants with unknown HER2/neu status
must have their HER2/neu status determined locally. Participants with HER2/neu
negative are eligible.
Participants with HER2/neu positive tumors must have documentation of disease
progression on treatment containing an approved HER2 targeted therapy to be
eligible.
Prior anticancer therapy (For dose expansion Part 2 only):
I 09. Participants in Cohort A: Participants must have received at least 1
systemic therapy for the metastatic setting and must not be amenable to the
available SOC.
Participants in Cohort B: Participants who have received at least 1 prior
anticancer therapy, including an anti-PD1/PD-L1 containing regimen, and for
whom have progressed
after a primary or secondary resistance to an anti-PD1/PD-L1.
Primary resistance: participant must have experienced PD or SD lasting <6
months since the initiation of the anti-PD1/PD-L1 inhibitor-based treatment and
the participant must have received PD1/PD-L1 for at least 6 weeks. Radiographic
confirmation of the PD must be documented after a minimum of 4 weeks after the
initial identification of progression, unless: 1) investigator confirms
clinical progression/deterioration attributed to PD, or 2) the first
radiographic assessment indicated critical tumor growth by imaging (size or
location).
Secondary resistance: participants must have experienced PD, either during or
within 3 months of discontinuing treatment with an anti-PD1 based therapy,
occurring after previous clear benefit (any complete [CR] or partial response
[PR]), or after previous SD of >6 months. There is no requirement for
radiographic confirmation of the progression.
I 10. Participants in Cohort C: Participants should have failed or relapsed
after at least 1 prior line of treatment, which does not include an
anti-PD1/PD-L1-based treatment.
Measurable Disease:
I 11. At least 1 measu
E 01. Eastern Cooperative Oncology Group (ECOG) performance status of >=2.
E 02. Predicted life expectancy <=3 months.
E 03. For participants with HCC- Cohort B (Part 2): Child Pugh Class B or C
liver score. Participants with Child Pugh Class B-7 score are allowed for Part
1.
E 04. Diagnosed of any other malignancies, either progressing or requiring
active treatments, within 2 years prior to enrollment, except for basal cell
carcinoma or squamous cell carcinoma of the skin, which are in-situ
malignancies, as well as superficial bladder carcinoma, or low risk prostate
cancer, and any tumors that have been deemed as effectively treated with
definitive local control.
E 05. Active brain metastases or leptomeningeal metastases:
• Participants with previously treated brain metastases are eligible, provided
they are clinically stable for at least 4 weeks with no evidence of new or
enlarging brain metastases, and have not received corticosteroids for at least
2 weeks prior to the first IMP administration.
• Participants with asymptomatic brain metastases (ie, no neurological
symptoms, no requirements for corticosteroids, and no lesion >1.5 cm) are
eligible but will require regular imaging of the brain at the site of the
disease.
E 06. History of treatment-related immune-mediated (or immune-related) AEs from
immune modulatory agents (including but not limited to anti-PD1/PD-L1 agents
and anti-cytotoxic T lymphocyte associated protein 4 monoclonal antibodies)
that caused permanent discontinuation of the agent, or that were Grade 4 in
severity, or have not resolved to Grade <=1.
E 07. Has any condition requiring ongoing/continuous corticosteroid therapy
(>10 mg prednisone/day or an anti-inflammatory equivalent) within 1 week prior
to the first dose of the study medicine. Physiologic replacement doses are
allowed even if they are >10 mg of prednisone/day or equivalent, as long as
they are not being administered for immunosuppressive intent. Inhaled or
topical steroids are permitted, provided that they are not for treatment of an
autoimmune disorder. Note: Participants who require a brief course of steroids
(up to 2 days in the week before enrollment) or physiologic replacement are
eligible to be enrolled in the study.
E 08. Any clinically significant cardiac (including valvular) or vascular
(thromboembolic disorders) disease, within 6 months prior to the first IMP
administration, such as:
• Congestive heart failure (New York Heart Association Class II to IV, or left
ventricular ejection fraction <50%).
• Increased troponin (higher than upper limit of normal [ULN] per local
laboratory) at screening. Participants with a higher troponin may be allowed
upon cardiologist consultation and discussion with the Study Medical Monitor on
a case-by-case basis.
• Unstable or poorly controlled angina, myocardial infarction, coronary artery
revascularization procedure (eg, coronary artery bypass graft, percutaneous
coronary intervention).
• Transient ischemic attack, cerebral infarction (stroke), symptomatic
pulmonary embolism, and peripheral artery revascularization procedure.
• Uncontrolled cardiac arrhythmia requiring medication (>= Grade 2, according to
the NCI-CTCAE V5.0).
E 09. History of congenital long QT syndrome, torsades de pointes or prolonged
QTc interval >48
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- Presence of dose limiting toxicities (DLTs) in Cycles 1 and 2<br /><br>- Presence of treatment-emergent adverse events (TEAEs)<br /><br>- Serious adverse events (SAEs)<br /><br>- Presence of TEAEs, SAEs, and lab abnormalities, according to the National<br /><br>Cancer Institute (NCI) Common Terminology Criteria for Adverse Events<br /><br>(CTCAE) Version 5.0 and American Society for Transplantation and Cellular<br /><br>Therapy (ASTCT) consensus grading<br /><br>- Objective response rate, which is defined as the proportion of participants<br /><br>who have a confirmed complete response (CR) or a partial response (PR),<br /><br>as the best overall response determined by the Investigator as per the Response<br /><br>Evaluation Criteria in Solid Tumors (RECIST) v1.1</p><br>
- Secondary Outcome Measures
Name Time Method