Phase 2, Single-arm Trial of BMS-986340 in Association With Nivolumab, Trifluridine/Tipiracil and Bevacizumab for Patients Refractory to Standard of Care Treatment and With Microsatellite-stable Colorectal Cancer

Eligibility Criteria

Participants with histologically or cytologically confirmed colorectal adenocarcinoma who have metastatic or locally advanced and unresectable disease and are microsatellite stable (MSS).

Participants must have measurable disease as defined by RECIST version 1.1.

Participants must be refractory or intolerant to fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab (if eligible), and cetuximab or panitumumab (if eligible).

o Regimens received in the adjuvant setting with recurrence within 6 months would be considered eligible treatments.

Age ≥18 years. Because no dosing or adverse event data are currently available on the use of BMS-986340 in combination with Nivolumab in participant s \<18 years of age, children are excluded from this study.

ECOG performance status ≤2 (Karnofsky ≥60%,).

Participants must have adequate organ and marrow function as defined below:

* absolute neutrophil count ≥1,500/mcL

* Hemoglobin ≥9 g/dL

* platelets ≥100,000/mcL

* AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN (unless if liver function abnormalities are due to underlying liver metastasis, AST (SGOT) and ALT (SGPT) ≤ 5 x ULN)

* Total serum bilirubin \<1.5 x upper limit of normal (ULN) (unless Gilbert disease confirmed)

* Creatinine ≤ institutional ULN

For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

Since the teratogenicity of BMS-986340 is unknown, and other therapeutic agents are known to be teratogenic, women of child-bearing potential must agree to use highly effective contraception methods (as detailed below) prior to study entry, for the duration of study participation, and for 6 months after completion of BMS-986340 administration(Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114).

This includes all female participants, between the onset of menses and 55 years unless the participant presents with an applicable exclusionary factor which may be one of the following:

Postmenopausal Females. A postmenopausal state is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes. In addition, females under the age of 55 years must have a follicle stimulating hormone (FSH) level \>40 mIU/mL to confirm menopause. Females treated with hormone replacement therapy (HRT) may require a washout period to obtain physiologic FSH levels, depending on the HRT method used:

One week minumum for vaginal hormonal products (rings, creams, gels).

Four weeks minimum for transdermal products.

Eight weeks minimum for oral products.

History of hysterectomy or bilateral salpingo-oophorectomy.

Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).

History of bilateral tubal ligation or another surgical sterilization procedure.

* Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

* Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial 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.

* Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 6 months after completion of BMS-986340 administration.

* Ability to understand and the willingness to sign a written informed consent document and to comply with study visits.

What this study is about