Phase 1 Study Of SAR445877 In Combination With FOLFOX6 And Bevacizumab As First-Line Treatment For Microsatellite Stable Metastatic Colorectal Cancer

Eligibility Criteria

1. Ability to understand and willingness to sign informed consent form prior to initiation of the study and any study procedures.

2. Capable of and willing to comply with scheduled visits, treatment plans, laboratory tests, and other study-related tests and procedures.

3. Age ≥18 years.

4. Participants with histologically documented CRC with metastatic disease who have not received prior treatment in the metastatic setting. Participants who have received adjuvant FOLFOX must be 6 months from treatment at the time of enrollment.

5. CRC documented as MSS by immunohistochemistry, next-generation sequencing, or polymerase chain reaction assay at any time prior to screening.

6. Measurable disease per the RECIST v1.1.

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

8. Adequate organ and marrow function as defined below within 28 days of study treatment initiation:

* Hemoglobin \>9.0 g/dL

* Absolute neutrophil count ≥1500/mL

* Platelets ≥100,000/mL

* Total bilirubin ≤1.5 × institutional upper limit of normal (ULN). Documented Gilbert syndrome is allowed if total bilirubin is ≤3 × ULN.

* Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5 × institutional ULN. Transaminases up to 3 × ULN in the presence of liver metastases.

* Estimated glomerular filtration rate ≥50 mL/min/1.73 m² (Modification of Diet in Renal Disease Formula)

* For participants not receiving therapeutic anticoagulation: international normalized ratio or activated partial thromboplastin time ≤1.5 × ULN. For participants receiving therapeutic anticoagulation: stable anticoagulant regimen.

9. Life expectancy ≥ 3 months.

10. The effects of SAR445877 and FOLFOX/bevacizumab on the developing human fetus are unknown. For this reason, women of childbearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of the study treatment period, and for 9 months after completion of study treatment.

(Refer to Pregnancy Assessment Policy MD Anderson Cancer Center \[MDACC\] Institutional Policy # CLN1114). WOCBP includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the participant presents with an applicable exclusionary factor which may be one of the following:

* Postmenopausal (no menses in ≥12 consecutive months)

* History of hysterectomy or bilateral salpingo-oophorectomy

* Ovarian failure (follicle-stimulating hormone and estradiol in menopausal range and have received whole pelvic radiation therapy)

* History of bilateral tubal ligation or another surgical sterilization procedure

* Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), intrauterine device, tubal ligation or hysterectomy, patient/partner post vasectomy, implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the duration of the study treatment period and the drug washout period is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

11. Male participants must agree to use adequate contraception throughout the duration of the study treatment period and for 6 months after the last dose of study treatment

12. WOCBP must have a negative serum pregnancy test within 3 days prior to first administration of study treatment.

What this study is about