Phase II Trial of Puxitatug Samrotecan (AZD8205) in Advanced, Recurrent or Metastatic (R/M) Aggressive Adenoid Cystic Carcinoma Subtype I (ACC-I)

NCT07162480 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2025-0803NCI-2025-06440
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

Phase II open label study designed to evaluate the efficacy and safety of P-Sam in patients with aggressive, solid, NOTCH mutant or p63 low (B7-H4 high) R/M ACC-I patients.

Conditions

Adenoid Cystic Carcinoma

Outcome Measures

Primary Outcomes (1)

• Safety and Adverse Events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (1)

P-Sam

EXPERIMENTAL

Participants will receive P-Sam at 2.4 mg/kg intravenously on D1 of a 21-day treatment cycle

Drug: P-Sam

Interventions

P-Sam DRUG

Given by IV

P-Sam

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥18 years with histology-proven advanced, or R/M ACC.
• Evidence of locally advanced disease not amenable to curative intent surgery or radiotherapy, or recurrent/metastatic disease
• ACC-I subtype defined by at least one of the following:
• Presence of an activating NOTCH mutation per in-house or any CLIA-certified or commercially available next-generation sequencing assay
• Solid histology and clinical course characterized by \< 3 years from diagnosis to initial recurrence or progression or de novo metastatic disease with extra-pulmonary metastasis
• Negative TP63 tumor expression by IHC (\<10% of tumor cells)
• Measurable disease per RECIST 1.1
• Performance status ECOG of 0 or 1
• Patient has provided informed consent.
• Adequate bone marrow, hepatic, and renal function with the most recent laboratory assessments 8. Contraceptive use by the participant or the participant's partner should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• (a) Male participants: (i) Non-sterilized male participants who are sexually active with a female partner of childbearing potential must use a male condom (plus spermicide, if available) from enrollment throughout the study and for 8 months following the last dose of study drug. It is strongly recommended for the female partner of a male participant to also use a highly effective method of contraception throughout this period, as described in Table 3. In addition, male participants must refrain from sperm donation while on study and for 8 months (5 half-lives plus 6 months) following the last dose of study drug.
• (b) Female participants: (i) Females of childbearing potential must have a negative urine or serum pregnancy test prior to receiving the first dose of study drug. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• (ii) Female participants of childbearing potential who are sexually active with a non-sterilized male partner must agree to use one highly effective method of birth control (defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly, from enrollment throughout the study and for 8 months following the last dose of study drug. It is strongly recommended for the male partner of a female participant to also use male condom (plus spermicide, if available) throughout this period. Cessation of contraception after this point should be discussed with a responsible physician.
• \. Patients can be treatment-naïve or have received up to 3 lines of prior systemic therapy in the setting ofR/M disease, however, a maximum of two prior lines of chemotherapy or antibody-drug conjugate (ADC) are allowed. Exceptions include prior B7-H4-targeting ADC or any prior agent with a topoisomerase inhibitor

You may not qualify if:

• Treatment with any of the following as detailed below in Table 2:
• Table 2 . Washout period from prior therapies Treatment Washout period Nitrosourea or mitomycin C Within 6 weeks prior to the first dose of study intervention Any investigational agents or study drugs from a previous clinical study Within 5 half-lives or 28 days (whichever is shorter) prior to the first dose of study drug Any other anticancer treatment Within the following time periods prior to the first dose of study intervention: Cytotoxic treatment: 21 days Non-cytotoxic drugs: 21 days or 5 half-lives (whichever is shorter) Biological products including immuno-oncology agents: 28 days Radiotherapy Wide field of radiation (including whole brain radiotherapy) within 4 weeks or limited field radiotherapy (including stereotactic radiotherapy or gamma-knife) for palliation is allowed up to 14 days prior to the first dose of study intervention. Participants who have not recovered from radiotherapy-related toxicity will not be eligible Major surgery (as defined by the Investigator) At least 28 days prior to the first dose of study intervention
• Unresolved toxicities of Grade ≥ 2 (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE version 5.0) from prior therapy (excluding vitiligo, alopecia, endocrine disorders that are controlled with replacement hormone therapy, and lymphopenia unless it is accompanied by clinical signs of infection or the indication for prophylaxis with antibiotic/antiviral/antifungal therapy). Participants with chemotherapy-induced Grade 2 neuropathy may be eligible at discretion of the Investigator.
• Active infection, including tuberculosis, SARS-CoV-2, and known infections with hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency. Participants with a past or resolved HBV/HCV infection are eligible if all the following criteria are met:
• Negative for HBsAg and positive for total hepatitis B core antibody (anti-HBc) or Positive for HBsAg, but for \> 6 months have had normal transaminases and HBV DNA levels between 0-2000 IU/mL (inactive carrier state) and willing to start and maintain antiviral treatment for at least the duration of the study.
• HBV DNA levels \> 2000 IU/mL but on prophylactic antiviral treatment for the past 3 months and will maintain the antiviral treatment during the study.
• Participants testing positive for HCV antibody are eligible only if the polymerase chain reaction test result is negative for HCV RNA.
• Has a history of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
• Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement or prior pneumonectomy (complete) or require supplemental oxygen (including intermittent or discretionary use).
• Patients with history of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML (as determined by prior diagnostic investigation). Specific screening for MDS/AML is not required.
• Participants with any of the following cardiac criteria:
• History of clinically significant arrhythmia (such as multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (NCI CTCAE version 5.0 Grade 3); symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia.
• NOTE: abnormalities in serum electrolytes that can increase the risk of arrhythmic events (ie, sodium, potassium, calcium, magnesium) should be corrected before starting the study intervention
• Uncontrolled hypertension.
• Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention, or coronary artery bypass grafting within 6 months of the start of study treatment.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• AstraZeneca: collaborator

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Carcinoma, Adenoid Cystic

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Renata Ferrarotto, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Renata Ferrarotto, MD

CONTACT

(713) 745-6774; rferrarotto@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2025
• First Posted: September 9, 2025
• Study Start: April 29, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2031
• Last Updated: May 4, 2026

Record last verified: 2026-05

Locations

US (1)