Clinical trial NCT04717375: Study of SAR444881 Administered Alone and in Combination With Other Therapeutics in Participants With Advanced Solid Tumors
Official title: A Phase 1/2, Dose Escalation, Dose Expansion, and Dose Optimization Study of the Safety, Tolerability, and Anti-tumor Activity of SAR444881 Administered Alone and in Combination With Pembrolizumab, Cetuximab and/or Chemotherapy in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cancer
Neoplasm
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-01-22
Enrollment: 456
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The study will enroll advanced cancer patients with unresectable or metastatic disease who are refractory to or are not candidates for standard approved therapy. The study will be comprised of two parts - a dose escalation phase (Part 1) and a dose optimization/expansion phase (Part 2). Part 1 is comprised of three sub-parts: SAR444881 administered alone (Sub-Part 1A), SAR444881 administered in combination with pembrolizumab (Sub-Part 1B), and SAR444881 administered in combination with cetuximab (Sub-Part 1C). Part 2 is composed of two sub-parts: a dose optimization part where up to two doses of SAR444881 per indication are administered in combination with pembrolizumab, cetuximab, and/or carboplatin and pemetrexed (Sub-Part 2A); and a dose expansion part where SAR444881 is administered alone (Sub-Part 2B). In Sub-Part 2A, a two-stage design will be implemented to conduct dose optimization for each indication with combination therapy- Stage 1 (Preliminary Assessment) and Stage 2 (Randomization). Study is non-randomized except Stage 2 of Sub-Part 2A which will use randomization.

Detailed description: Estimated Study Duration:

Dose Escalation (Part 1): Approximately 34 months Dose Optimization/Expansion (Part 2): Approximately 28 months

Eligibility criteria: Inclusion Criteria:

* Patients with unresectable or metastatic disease who are refractory to or are not candidates for standard approved therapy
* Histologic confirmation of malignancy
* Measurable disease per RECIST v1.1
* Eastern Cooperative Oncology Group Performance Status (ECOG) of 0 or 1
* Participants must have adequate organ function as defined by laboratory tests
* Part 1: Following tumor types: Breast cancer, cervical cancer, colorectal cancer, adenocarcinoma or squamous cell carcinoma of the esophagus, gastric or gastroesophageal junction adenocarcinoma, squamous cell carcinoma of the head and neck, hepatobiliary cancers (hepatocellular carcinoma (HCC), gallbladder cancer, cholangiocarcinoma), non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the skin, pancreatic adenocarcinoma, ovarian cancer or urothelial carcinoma
* Part 2: Following tumor types: Squamous cell carcinoma of the head and neck, Gastric or gastroesophageal junction adenocarcinoma, non-squamous non-small cell lung cancer, non-small cell lung cancer, colorectal carcinoma (CRC) any RAS, and/or Cholangiocarcinoma

Exclusion Criteria:

* Active, known or suspected autoimmune disease
* Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications
* Brain or leptomeningeal metastases
* Known history of positive test for HIV
* Non-HCC patients: acute or chronic hepatitis B virus (HBV) or hepatitis C virus (HCV); HCC patients: untreated active HBV or dual infection with HBV/HCV
* Participants after solid organ or allogeneic hematopoietic stem cell transplant
* History of life-threatening toxicity related to prior immune therapy
* History of life-threatening toxicity related to prior cetuximab or other anti-EGFR antibodies (for Sub-Part 1C)
* Unstable or deteriorating cardiovascular disease within the previous 6 months
* Any major surgery within 4 weeks of study drug administration
* Prior/Concomitant Therapy:
* Cytotoxic/Non-cytotoxic anti-cancer agents, unless at least 4 weeks have elapsed from last dose
* Use of other investigational drugs within 28 days
* Prior treatment with macrophage or natural killer (NK) cells activating therapies
* Administration of a live attenuated vaccine within 28 days

The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

Primary outcomes:
measure: Part 1: Incidence of treatment-emergent adverse events (TEAEs) dose limiting toxicities (DLT)
timeFrame: Cycle 1 (28 days)
measure: Part 1: Incidence of treatment-emergent adverse events and serious adverse events
timeFrame: Through study completion, an average of 5 months
measure: Part 2: Objective Response Rate (ORR) per RECIST v1.1
timeFrame: Through study completion, an average of 3 months
Secondary outcomes:
measure: Part 1: Objective Response Rate (ORR) per RECIST v1.1
timeFrame: Through study completion, an average of 3 months
measure: Part 1: Maximum observed plasma concentration [Cmax]
timeFrame: Through study completion, an average of 2 months
measure: Part 1: Serum concentration at the end of the dosing interval (Ctrough)
timeFrame: Through study completion, an average of 2 months
measure: Part 1: time of maximum observed serum concentration (Tmax)
timeFrame: Through study completion, an average of 2 months
measure: Part 1: Terminal elimination half-life [T1/2]
timeFrame: Through study completion, an average of 2 months
measure: Part 1: Area under the plasma concentration-time curve [AUC]
timeFrame: Through study completion, an average of 2 months
measure: Part 1: Incidence of anti-drug antibodies (ADA)
timeFrame: Through study completion, an average of 5 months
measure: Part 2: Progression Free Survival (PFS)
timeFrame: Up to 24 months
measure: PFS rate
timeFrame: At 3, 6, 9, and 12 months, and up to 24 months
measure: Part 2: Duration of Response
timeFrame: Through study completion, an average of 6 months
measure: Part 2: Incidence of treatment-emergent adverse events and Serious Adverse Events
timeFrame: Through study completion, an average of 6 months
measure: Part 2: Cmax
timeFrame: Through study completion, an average of 3 months
measure: Part 2: Ctrough
timeFrame: Through study completion, an average of 3 months
measure: Part 2: Tmax
timeFrame: Through study completion, an average of 3 months
measure: Part 2: T1/2
timeFrame: Through study completion, an average of 3 months
measure: Part 2: AUC
timeFrame: Through study completion, an average of 3 months
measure: Part 2: Incidence of ADA
timeFrame: Through study completion, an average of 6 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital- Site Number : 8400003
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center- Site Number : 8400002
state: California
city: Aurora
country: United States
facility: University of Colorado- Site Number : 8400012
state: Colorado
city: New Haven
country: United States
facility: Smilow Cancer Center at Yale-New Haven- Site Number : 8400001
state: Connecticut
city: Clermont
country: United States
facility: Clermont Oncology Center- Site Number : 8400005
state: Florida
city: Orange City
country: United States
facility: Mid Florida Hematology and Oncology Center- Site Number : 8400006
state: Florida
city: Des Moines
country: United States
facility: Mercy Cancer Center - MercyOne Richard Deming Cancer Center- Site Number : 8400011
state: Iowa
city: Louisville
country: United States
facility: Norton Cancer Institute - Downtown Women's Cancer Center- Site Number : 8400004
state: Kentucky
city: Rochester
country: United States
facility: Mayo Clinic Hospital Rochester- Site Number : 8400007
state: Minnesota
city: Barrie
country: Canada
facility: Investigational Site Number : 1240001
state: Ontario
city: Sherbrooke
country: Canada
facility: Investigational Site Number : 1240003
state: Quebec
city: Haifa
country: Israel
facility: Investigational Site Number : 3760004
city: Jerusalem
country: Israel
facility: Investigational Site Number : 3760005
city: Petah Tikva
country: Israel
facility: Investigational Site Number : 3760001
city: Ramat Gan
country: Israel
facility: Investigational Site Number : 3760003
city: Tel Aviv
country: Israel
facility: Investigational Site Number : 3760002
city: London
country: United Kingdom
facility: Investigational Site Number : 8260003
state: London, City Of
city: Leeds
country: United Kingdom
facility: Investigational Site Number : 8260002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Mandel I, Haves Ziv D, Goldshtein I, Peretz T, Alishekevitz D, Fridman Dror A, Hakim M, Hashmueli S, Friedman I, Sapir Y, Greco R, Qu H, Nestle F, Wiederschain D, Pao L, Sharma S, Ben Moshe T. BND-22, a first-in-class humanized ILT2-blocking antibody, promotes antitumor immunity and tumor regression. J Immunother Cancer. 2022 Sep;10(9):e004859. doi: 10.1136/jitc-2022-004859.