Study to Evaluate the Efficacy of Zanzalintinib in the Treatment of Relapsed or Metastatic Adenoid Cystic Carcinomas of the Head and Neck

Inclusion Criteria: * Patient must have signed a written informed consent form prior to any trial specific procedures * Patient ≥18 years of age on day of signing informed consent * Adenoid Cystic Carcinoma (histologically proven) originating from the head and neck region in relapse and/or metastatic, not suitable for local therapy * Subjects must have at least 1 lesion measurable per RECIST v1.1 Criteria, with MRI or CT-scan * Patients with significant disease progression diagnosed within 3 months prior to enrollment, defined by radiological progression according to RECIST 1.1 determined by the comparison of 2 CT scans or 2 MRIs separated by a maximum of 6 months. * Performance Status 0-1 * Subjects must have biopsiable tumor at screening. The use of recent archived biopsy at screening could be discussed with the coordinating team if there was no treatment between the biopsy and the inclusion. * Recovery to baseline or ≤ Grade 1 severity (National Cancer Institute - common terminology criteria for adverse events version 6.0 \[NCI-CTCAE v6.0\]) from adverse events (AEs), including immune-related adverse events (irAEs), related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy (eg, physiological replacement of corticosteroid). Low-grade or controlled toxicities such as alopecia, ≤ Grade 2 hypomagnesemia, ≤ Grade 2 neuropathy are permitted). * Adequate bone marrow function within 14 days before first dose of study treatment (absolute neutrophil count \> 1,500 cells/mm3, platelets \> 100,000 cells/mm3, Hb \> 9g/dl, INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.2 x upper limit of normal (ULN). * Adequate liver function within 14 days before first dose of study treatment (total bilirubin ≤ 1.5 x UNL (for subjects with Gilbert's disease ≤ 3 x ULN), AST, ALT and ALP ≤ 3 x UNL or \< 5 x UNL in case of hepatic metastasis). * Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 40 mL/min (≥ 0.67 mL/sec) using the Cockcroft Gault equation. * Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) creatinine * Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures * Patients must be affiliated to a Social Security System * Women of childbearing potential must have a negative serum β-HCG pregnancy test within 7 days and/or negative urine pregnancy test within 48 hours prior to the administration of the first study treatment. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes. In addition, females \< 55 years-of-age must have a serum follicle stimulating hormone \[FSH\] level \> 40 mIU/mL to confirm menopause). Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff. * Sexually active fertile subjects and their partners must agree to use highly effective method of contraception during the course of the study and through 186 days after the last dose of zanzalintinib for women of childbearing potential (WOCBP) or through 96 days after the last dose of zanzalintinib for men (whichever is later). An additional contraceptive method, such as a barrier method (eg, condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods. Exclusion Criteria: * Prior treatment with zanzalintinib or with another inhibitor of VEGFR * Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment. * Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment. * Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible. * Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study treatment. Note: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment. Note: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed. * Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin inhibitors ) and platelet inhibitors (eg, clopidogrel). Allowed anticoagulants are the following: 1. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH). 2. Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen. Note: Subjects must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to first dose of study treatment, whichever is longer. * Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment. * The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: a) Unstable of deteriorating cardiovascular disorders: i. Congestive heart failure New York Heart Association Class 3 or 4, class 2 or higher, unstable angina pectoris, new-onset angina, serious cardiac arrhythmias (eg, ventricular flutter, ventricular fibrillation, Torsades de pointes). ii. Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment. iii. Stroke (including transient ischemic attack \[TIA\]), myocardial infarction, or other clinically significant arterial thrombotic and/or ischemic event within 6 months before first dose of study treatment. iv. Pulmonary embolism (PE) or deep vein thrombosis (DVT) or other prior clinically significant venous events within 3 months before first dose of study treatment. Note: Subjects with a diagnosis of DVT within 6 months are allowed if asymptomatic and stable at screening and are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen. Note: Subjects who don't require prior anticoagulation therapy may be eligible but must be discussed and approved by the investigator. v. Prior history of myocarditis. b) Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i. Tumors invading the GI-tract from external viscera ii. Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis iii. Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months before first dose unless cause of obstruction is definitively managed and subject is asymptomatic iv. Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose of study treatment. v. Known gastric or esophageal varices vi. Ascites, pleural effusion, or pericardial fluid requiring drainage in last 4 weeks * Clinically significant hematuria, hematemesis, or hemoptysis of \> 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose of study treatment. * Symptomatic cavitating pulmonary lesion(s) or endobronchial disease (asymptomatic or radiated lesions allowed) * Lesions invading major blood vessel including, but not limited to, inferior vena cava, pulmonary artery, or aorta. Note: Subjects with intravascular tumor extension (eg, tumor thrombus in renal vein or inferior V. cava) may be eligible following investigator approval. * Other clinically significant disorders that would preclude safe study participation. 1. Active infection requiring systemic treatment. Note: Prophylactic antimicrobial treatments (antibiotics, antimycotic, antiviral) are allowed. 2. Known infection with acute or chronic hepatitis B or C, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness except for subjects meeting all of the following criteria: (1) on stable anti-retroviral therapy; (2) CD4+ T cell count ≥ 200/µL; and (3) an undetectable viral load. Note: HIV testing will be performed at screening if and as required by local regulation. Note: To be eligible, participants taking CYP inhibitors (eg, zidovudine, ritonavir, cobicistat, didanosine) or CYP3 inducers (efavirenz) must change to a different regimen not including these drugs 7 days prior to initiation of study treatment. Anti-retroviral therapies (ART) must have been received for at least 4 weeks prior to the first dose. Note: CD4+ T cell counts, and viral load are monitored per standard of care by the local health care provider. 3. Serious non-healing wound/ulcer/bone fracture. Note: non-healing wounds or ulcers are permitted if due to tumor-associated skin lesions. 4. Malabsorption syndrome. 5. Pharmacologically uncompensated, symptomatic hypothyroidism. 6. Moderate to severe hepatic impairment (Child-Pugh B or C). 7. Requirement for hemodialysis or peritoneal dialysis. 8. History of solid organ or allogeneic stem cell transplant. * Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks prior to first dose of study treatment. Prior laparoscopic surgeries (ie nephrectomy) within 4 weeks prior to first dose of study treatment. Minor surgery (eg, simple excision, tooth extraction) within 5 days before first dose of study treatment. Complete wound healing from major or minor surgery must have occurred at least prior to first dose of study treatment. Note: Fresh tumor biopsies should be performed at least 5 days before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgical procedures, including biopsies, are not eligible. \- Corrected QT interval calculated by the Fridericia formula (QTcF) \> 480 ms within 14 days per electrocardiogram (ECG) before first dose of study treatment. Note: Triplicate ECG evaluations will be performed and the average of these 3 consecutive results for QTcF will be used to determine eligibility. * History of psychiatric illness likely to interfere with ability to comply with protocol requirements or give informed consent. * Inability to swallow tablets or ingest a suspension either orally or by a nasogastric (NG) or gastrostomy (PEG) tube. * Previously identified allergy or hypersensitivity to components of the study treatment formulations. * Another malignancy that requires active therapy and in the opinion of the Investigator would interfere with monitoring of radiologic assessments of response to Investigational Product, within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy. Incidentally diagnosed prostate cancer is allowed if assessed as stage ≤ T2N0M0 and Gleason score ≤ 6. * Other conditions, which in the opinion of the Investigator, would compromise the safety of the patient or the patient's ability to complete the study. * Pregnant or breast-feeding women. * Person deprived of their liberty or under protective custody or guardianship