AMTEC IIT: Phase 2 Multiarm Study in TNBC

NCT03801369 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: STUDY00018504NCI-2019-00388STUDY00028065
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II study assesses the efficacy of the combination of olaparib with durvalumab, selumetinib, or capivasertib or ceralasertib alone in the treatment of patients with metastatic triple negative breast cancer (TNBC). Olaparib may stop growth of tumor cells by inhibiting some of the enzymes (ADP ribose polymerase \[PARP\]) needed for cell growth. Durvalumab, a monoclonal antibody, inhibits the growth and spread of tumors by stimulating the patient's antitumor immune response. Selumetinib, capivasertib, and ceralasertib are inhibitor drugs that may stop the growth of tumor cells by blocking some of the enzymes (MEK, AKT, ATR) needed for cell growth. Giving olaparib together with durvalumab, selumetinib, or capivasertib or giving ceralasertib alone may provide an effective method to treat patients with metastatic triple negative breast cancer.

Conditions

Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Using the efficacy analysis set, the estimate of ORR will be measured independently for each treatment arm and reported with 95% exact confidence interval. Participants who, within their respective treatment arm, achieve a complete response (CR) or a partial response (PR) that is confirmed on a second scan at least 4 weeks later on the current protocol will be qualified as achieving a response, and will count towards the ORR measurement.

  End of treatment (Up to 24 months)

Secondary Outcomes (6)

• Clinical Benefit Rate (CBR)

  End of treatment (Up to 24 months)

• Duration of Response (DOR)

  Duration of response was calculated from date of PR/CR (whichever occurred earlier) to EOT.

• Progression-free Survival (PFS)

  Progression or death (any cause) up to 1 year post treatment

• Overall Survival (OS)

  Death (any cause) up to 1 year post treatment

• Incidence of Grade 3+ Acute Toxicity: # of Occurrences

  Up to 3 months post treatment

Other Outcomes (2)

• Change in Quality of Life (QOL) as Measured by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)

  Baseline to end of treatment (Up to 24 months)

• Change in QOL as Measured by EORTC QLQBR23

  Baseline to end of treatment (Up to 24 months)

Study Arms (4)

Arm I (olaparib, durvalumab)

EXPERIMENTAL

Patients receive olaparib PO BID on days 1-28 of each cycle and durvalumab intravenously (IV) over 1 hour on day 1 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.

Procedure: Biopsy; Biological: Durvalumab; Drug: Olaparib; Other: Quality-of-Life Assessment

Arm II (olaparib, selumetinib)

EXPERIMENTAL

Patients receive olaparib PO BID on days 1-28 of each cycle and selumetinib PO BID on days 1-28 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.

Procedure: Biopsy; Drug: Olaparib; Other: Quality-of-Life Assessment; Drug: Selumetinib

Arm III (olaparib, capivasertib)

EXPERIMENTAL

Patients receive olaparib PO BID on days 1-28 of each cycle and capivasertib PO BID 4 days on and 3 days off of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.

Procedure: Biopsy; Drug: Capivasertib; Drug: Olaparib; Other: Quality-of-Life Assessment

Arm IV (ceralasertib)

EXPERIMENTAL

Patients receive ceralasertib PO BID on days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients deriving clinical benefit from treatment may, at the investigator's discretion and in the absence of disease progression or unacceptable toxicity, continue on therapy beyond the planned 13 cycles.

Procedure: Biopsy; Drug: Ceralasertib; Other: Quality-of-Life Assessment

Interventions

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (olaparib, durvalumab); Arm II (olaparib, selumetinib); Arm III (olaparib, capivasertib); Arm IV (ceralasertib)

Selumetinib DRUG

Given PO (orally)

Also known as: ARRY-142886, AZD6244, MEK Inhibitor AZD6244

Arm II (olaparib, selumetinib)

Ceralasertib DRUG

Given PO (orally)

Also known as: AZD6738

Arm IV (ceralasertib)

Durvalumab BIOLOGICAL

Given IV (infusion)

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Arm I (olaparib, durvalumab)

Olaparib DRUG

Given PO (orally)

Also known as: AZD 2281, AZD-2281, AZD2281, KU-0059436, Lynparza, PARP Inhibitor AZD2281

Arm I (olaparib, durvalumab); Arm II (olaparib, selumetinib); Arm III (olaparib, capivasertib)

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Arm I (olaparib, durvalumab); Arm II (olaparib, selumetinib); Arm III (olaparib, capivasertib); Arm IV (ceralasertib)

Capivasertib DRUG

Given PO (orally)

Also known as: AZD5363

Arm III (olaparib, capivasertib)

Eligibility Criteria

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

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document
• Participants are \>= 18 years old at time of informed consent.
• Metastatic TNBC, as defined by:
• Estrogen receptor (ER) and progesterone receptor (PR) negative as defined as ER \< 10% and PR \< 10% by immunohistochemistry according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines for hormone receptor testing
• HER2 non-amplified per ASCO/CAP guidelines, defined as:
• IHC score 0/1+
• IHC 2+ and in situ hybridization (ISH) non-amplified with a ratio of HER2 to CEP17 \< 2.0, and if reported, average HER2 gene copy number \< 4 signals/cells; or
• ISH non-amplified with a ratio of HER2 to CEP17 \<2.0, and if reported, average HER2 gene copy number \< 4 signals/cells
• Participants with or without germline BRCA mutated TNBC are eligible for study participation
• Participants must have at least one measurable site of disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 that is amenable to biopsy
• Prior therapies for metastatic breast cancer
• Frontline patients who have not received prior systemic therapy for metastatic breast cancer are eligible
• Patients who have received =\< 2 prior chemotherapy regimens for metastatic breast cancer are eligible
• Participants must have fully recovered from the acute toxic effects of all prior treatment to grade 1 or less, except alopecia which is allowed
• Participants must have a life expectancy \>= 16 weeks

You may not qualify if:

• Any concurrent anticancer treatment
• Individuals in the follow-up phase of a prior investigational study may participate as long as it has been 4 weeks since last dose of the previous investigational agent or device
• Concurrent use of hormonal therapy for non-cancer related conditions (e.g., hormone replacement therapy) is allowed
• Participant's with tumors showing androgen receptor (AR) \>= 80% by immunohistochemistry are excluded
• Other malignancy unless curatively treated with no evidence of disease for \>= 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), stage 1, grade 1 endometrial carcinoma. Participants with a personal history of treated early stage breast cancer whose natural history or treatment does not have the potential to interfere with the safety or efficacy endpoints of the trial, per investigator assessment, are eligible
• Participants with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML)
• Participant received prior anticancer therapy such as targeted therapies, or systemic chemotherapy or radiation (except for palliative reasons) within the past 3 weeks, or 5 half-lives, whichever is shorter, prior to first day of treatment
• Participants with known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Patients with brain metastases may participate provided they do not have symptomatic uncontrolled disease. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. (note: a scan to confirm the absence of brain metastases is not required)
• Patients with spinal cord compression are not eligible unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
• Patients with carcinomatous meningitis are not eligible
• Concomitant use of known strong CYP3A inhibitors (e.g., ketoconazole, posaconazole), or strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting study intervention treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
• Major surgery within 4 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
• Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
• Patients that are immunocompromised, including those with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness are not eligible for participation

Sponsors & Collaborators

• Gordon Mills, MD, PhD: lead
• AstraZeneca: collaborator
• Oregon Health and Science University: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

Related Publications (1)

• Sun C, Fang Y, Labrie M, Li X, Mills GB. Systems approach to rational combination therapy: PARP inhibitors. Biochem Soc Trans. 2020 Jun 30;48(3):1101-1108. doi: 10.1042/BST20191092.

  PMID: 32379297 DERIVED

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Biopsy; capivasertib; ceralasertib; durvalumab; Immunoglobulin G; Disulfides; olaparib; AZD 6244

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Results Point of Contact

• Title: Gordon Mills, MD, PhD
• Organization: Oregon Health & Science University - Knight Cancer Institute

millsg@ohsu.edu

503-346-4660

Study Officials

• Gordon Mills, MD, PhD

  OHSU Knight Cancer Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: IND Holder

Study Record Dates

• First Submitted: January 9, 2019
• First Posted: January 11, 2019
• Study Start: December 12, 2018
• Primary Completion: October 22, 2024
• Study Completion: December 23, 2024
• Last Updated: February 25, 2026
• Results First Posted: November 21, 2025

Record last verified: 2026-02

Locations

US (1)