AzTrials
AzTrials

HER2-negative Breast CancerPhase 1/2NCT05275777

A Phase Ib Safety lead-in, Followed by Phase II Trial of ADG106 in Combination With Neoadjuvant Chemotherapy in HER2 Negative Breast Cancer

A Phase 1/2 study testing ADG106, Doxorubicin and Cyclophosphamide in people with HER2-negative Breast Cancer and Advanced Solid Tumor, run by National University Hospital, Singapore at 1 site in Singapore.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This is an open label, lead in phase Ib dose confirmation study in patients with advanced solid tumors, followed by a phase II single arm study as neoadjuvant therapy in stage I-III HER2 negative breast cancer. Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
ADG106, Doxorubicin and Cyclophosphamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
1 siteSingapore
Study dates
19 May 2022to Feb 2030
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients may be included in the study only if they meet all of the following criteria:
  • All patients must sign an informed consent in accordance with local institutional guidelines.
  • 18 years and above of age.
  • Estimated life expectancy of at least 12 weeks.
  • Has recovered from acute toxicities from prior anti-cancer therapies (phase Ib).
  • a) Phase Ib: Patients with histologically or cytologically confirmed advanced or metastatic solid tumors who have radiological evidence of progressive disease on study entry that are deemed likely to benefit from either dose dense doxorubicin/ cyclophosphamide or weekly paclitaxel.
Show all 26Show fewer
  • There is no upper limit on the number of prior treatments provided all inclusion/ exclusion criteria are met. Hormone ablation therapy is considered an anti-cancer regimen. Radiation therapy and surgery are not considered anti-cancer regimens.
  • Prior receipt of immunotherapy is allowed. b) Phase II: Untreated stage I-III HER2 negative breast cancer patients who are planned for neoadjuvant chemotherapy followed by definitive breast cancer surgery.
  • Measurable disease by RECIST 1.1 criteria.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
  • Left ventricular ejection fraction of ≥ 50% for Cohort 1 in phase Ib and all patients in phase II.
  • Adequate bone marrow function and organ function within 2 weeks of study treatment.
  • Adequate hematologic function defined as:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
  • Platelets ≥ 100 x 109/L
  • Hemoglobin ≥ 9 x 109/L
  • Adequate hepatic function defined as:
  • Bilirubin < 1.5 times the upper limit of normal (ULN)
  • ALT or AST < 2.5 times ULN (or < 5 times ULN with presence of liver metastases)
  • Adequate renal function defined as:
  • Calculated creatinine clearance of ≥ 60 mL/min, calculated using the formula of Cockroft and Gault: (140-Age) x Mass (kg)/(72 x creatinine mg/dL); multiply by 0.85 if female.
  • Adequate coagulation function defined as:
  • Activated partial thromboplastin time (aPTT) ≤1.5 x ULN
  • International normalized ratio (INR) ≤1.5 x ULN (Exception: INR 2 to ≤3 x ULN is acceptable for patients on warfarin anticoagulation
  • Patients with reproductive potential must use an approved contraceptive method if appropriate (e.g., intrauterine device, birth control pills, or barrier device) during and for three months after the study. Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrolment.
  • Able to comply with study related procedures.

Who cannot join

  • Patients will be excluded from the study for any of the following reasons:
  • Treatment within the last 30 days with any investigational drug.
  • Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
  • Major surgery within 28 days of study drug administration.
  • Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
  • Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
Show all 25Show fewer
  • Active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol.
  • Subjects with a condition requiring systemic treatment with either corticosteroids (>10mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid >10mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
  • Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Active hepatitis B (positive hepatitis B surface antigen [HBsAg]) or HCV (hepatitis C virus) [positive HCV RNA])
  • Patients with past HBV infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible. HBV DNA must be obtained in these patients prior to randomization. HBV carriers or those patients requiring antiviral therapy are not eligible to participate.
  • Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
  • HBV carriers or those subjects receiving antiviral treatment of hepatitis B virus or Hepatitis C are not eligible.
  • Pregnancy.
  • Breast feeding.
  • Second primary malignancy that is clinically detectable at the time of consideration for study enrolment. The exception is patients in phase II with two or more primary invasive breast cancers that are both HER2 negative and where both cancers are amenable to repeated biopsy. In this case, each tumor will be biopsied and assessed separately for treatment response.
  • Symptomatic brain metastases.
  • History of significant neurological or mental disorder, including seizures or dementia.
  • Unable to comply with study procedures.
  • Phase II cohort: Prior treatment for locally advanced or metastatic breast cancer.
  • Patients with known underlying hemoglobinopathies (e.g., thalassemia). Note: patients without known hemoglobinopathies do not specifically need to be screened for hemoglobinopathies in the absence of clinical suspicion).
  • History of life-threatening hypersensitivity or known to be allergic to protein drugs or recombinant proteins or any ingredients contained in the ADG106 drug formulation (succinic acid, arginine, polysorbate 80 and hydrochloric acid).
  • Peripheral neuropathy grade ≥2.
  • Live viral vaccine therapies within 4 weeks prior to the first dose of study drug.

Trial locations and contacts

1 site in 1 country.

Singapore1 site

  • National University Hospital

    Singapore

Other trials in Singapore

About this study

Official title: A Phase Ib Safety lead-in, Followed by Phase II Trial of ADG106 in Combination With Neoadjuvant Doxorubicin and Cyclophosphamide Followed by Paclitaxel in Stage I-III HER2 Negative Breast Cancer

This is an open label, lead in phase Ib dose confirmation study in patients with advanced solid tumors, followed by a phase II single arm study as neoadjuvant therapy in stage I-III HER2 negative breast cancer.

Primary Objectives

Read more
  • To determine the safety profile of combination of ADG106 with dose dense doxorubicin/cyclophosphamide, and with weekly paclitaxel.
  • To determine the Recommended Phase 2 Dose (RP2D) of ADG106 in combination with dose dense doxorubicin/cyclophosphamide, and with weekly paclitaxel.
  • To evaluate biological changes on immunohistochemistry in HER2 negative breast cancer after treatment with ADG106 alone and in combination with chemotherapy.

Secondary Objectives

  • To determine the efficacy of combination of ADG106 with standard neoadjuvant combination chemotherapy in HER2 negative breast cancer: objective response rates.
  • To correlate tumor and plasma biomarkers with efficacy outcomes.
Read the detailed description

The phase Ib segment will be carried out with a standard 3+3 dose de-escalation design. Patients with advanced/ metastatic solid organ cancers will be enrolled in 2 parallel cohorts.

Cohort 1 will receive ADG106 in combination with dose dense doxorubicin/ cyclophosphamide (AC).

Cohort 2 will receive ADG106 in combination with weekly paclitaxel.

In the phase II portion, patients with stage I-III HER2 negative breast cancer planned for neoadjuvant chemotherapy will be enrolled. Patients will be treated with neoadjuvant chemotherapy (ddAC followed by paclitaxel for 12 weeks) combined with ADG106, before definitive breast cancer surgery

Keywords
HER2-negative Breast Cancer, ADG106, neoadjuvant doxorubicin and cyclophosphamide, paclitaxel

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ADG106Drug

    Administered as an intravenous infusion over 60-90 minutes in the initial cycle and over 30 minutes in subsequent cycle if well tolerated.

  • DoxorubicinDrug

    Also called Adriamycin

    Administered as an intravenous infusion.

  • CyclophosphamideDrug

    Also called Cytophosphane

    Administered as an intravenous infusion.

  • PaclitaxelDrug

    Also called Taxol

    Administered as an intravenous infusion.

Study groups in NCT05275777
Study groupRoleWhat they receive
ADG106 combined with dose dense Doxorubicin and Cyclophosphamide (Phase Ib)ExperimentalIntravenous ADG106 + 2 weekly doxorubicin and cyclophosphamide
Receives: Drug: ADG106; Drug: Doxorubicin; Drug: Cyclophosphamide
ADG106 combined with Paclitaxel (Phase Ib)ExperimentalIntravenous ADG106 + weekly paclitaxel
Receives: Drug: ADG106; Drug: Paclitaxel
ADG106 combined with dose dense Doxorubicin and Cyclophosphamide follow by Paclitaxel (Phase II)ExperimentalIntravenous ADG106 combined with two weekly doxorubicin and cyclophosphamide followed intravenous ADG106 combined with weekly paclitaxel
Receives: Drug: ADG106; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participant with treatment related toxicities

    Toxicities will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) toxicity grading version 5.0.

    Measured: From enrolment till 30 days after last dose of study treatment

  2. Histological response after neoadjuvant ADG106 + chemotherapy

    Biological changes on immunohistochemistry will be evaluated using paraffin-embedded tumor specimens.

    Measured: After 20 weeks of neoadjuvant chemotherapy

Secondary outcomes (7)

  1. Objective response rate in Phase Ib

    Complete and partial clinical response will be measured by RECIST 1.1.

    Measured: At the end of every 3 cycles up to 24 weeks, at the end of every 6 cycles after 24 weeks up to 60 weeks (each cycle is 2 weeks)

  2. Overall survival in Phase Ib

    Defined as the time from the date of study enrolment to the date of death from any cause, regardless of whether the death occurred during the study or following treatment discontinuation.

    Measured: From enrolment till date of death or final follow up visit (maximum 1 year after last treatment dose)

  3. Correlation of plasma biomarkers with efficacy outcome in Phase Ib

    Correlation of biomarkers with Objective Response Rate, Progression Free Survival, Overall Survival

    Measured: baseline, at the end of week 1, 2, 4, 6, 8, 10, 12, 14, 18, 30, 42, 54, 66

  4. Progression free survival in Phase Ib

    Defined as the time from the date of study enrolment to the first date of documented disease progression.

    Measured: From enrolment till disease progression or date of death or final follow-up visit (maximum 1 year after last treatment dose).

  5. Clinical response rate in Phase II

    Clinical response rate will be measured by calipers

    Measured: baseline, at the end of 2 weeks, 4 weeks, 8 weeks, 10 weeks, 12 weeks of treatment.

  6. Pathological complete response rate in Phase II

    Defined as any patient who demonstrates no histological evidence of invasive tumor in the primary breast site as well as in resected axillary lymph nodes.

    Measured: after 20 weeks neoadjuvant chemotherapy

  7. Relapse free survival in Phase II

    Defined as the time from the date of study enrolment to the first date of documented disease relapse.

    Measured: From enrolment to final follow up visit (maximum 6 years from last treatment dose)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Mar 2022
  2. Study start19 May 2022
  3. Primary completionDec 2027 (estimated)
  4. Study completionFeb 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Phase Ib: A 3+3 dose escalation design will be used to determine the RP2D dose of ADG106 in combination with ddAC and paclitaxel respectively. Phase II: ADG106 will be combined with ddAC followed by paclitaxel as neoadjuvant chemotherapy in patients with stage I-III HER2 negative breast cancer.
Masking
None (open label)
Enrolment
66 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05275777
Sponsor's protocol ID
ADG106-T6002
Status last verified
Jul 2025
First submitted
9 Feb 2022
Last updated
25 Jul 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Ding Y, Ding K, Yang H, He X, Mo W, Ding X. Does dose-dense neoadjuvant chemotherapy have clinically significant prognostic value in breast cancer?: A meta-analysis of 3,724 patients. PLoS One. 2020 May 29;15(5):e0234058. doi: 10.1371/journal.pone.0234058. eCollection 2020.

    PubMed 32470093

  • Hammerl D, Smid M, Timmermans AM, Sleijfer S, Martens JWM, Debets R. Breast cancer genomics and immuno-oncological markers to guide immune therapies. Semin Cancer Biol. 2018 Oct;52(Pt 2):178-188. doi: 10.1016/j.semcancer.2017.11.003. Epub 2017 Nov 6.

    PubMed 29104025

  • Nanda R, Liu MC, Yau C, Shatsky R, Pusztai L, Wallace A, Chien AJ, Forero-Torres A, Ellis E, Han H, Clark A, Albain K, Boughey JC, Jaskowiak NT, Elias A, Isaacs C, Kemmer K, Helsten T, Majure M, Stringer-Reasor E, Parker C, Lee MC, Haddad T, Cohen RN, Asare S, Wilson A, Hirst GL, Singhrao R, Steeg K, Asare A, Matthews JB, Berry S, Sanil A, Schwab R, Symmans WF, van 't Veer L, Yee D, DeMichele A, Hylton NM, Melisko M, Perlmutter J, Rugo HS, Berry DA, Esserman LJ. Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer: An Analysis of the Ongoing Phase 2 Adaptively Randomized I-SPY2 Trial. JAMA Oncol. 2020 May 1;6(5):676-684. doi: 10.1001/jamaoncol.2019.6650.

    PubMed 32053137

  • Mittendorf EA, Zhang H, Barrios CH, Saji S, Jung KH, Hegg R, Koehler A, Sohn J, Iwata H, Telli ML, Ferrario C, Punie K, Penault-Llorca F, Patel S, Duc AN, Liste-Hermoso M, Maiya V, Molinero L, Chui SY, Harbeck N. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet. 2020 Oct 10;396(10257):1090-1100. doi: 10.1016/S0140-6736(20)31953-X. Epub 2020 Sep 20.

    PubMed 32966830

  • Schmid P, Cortes J, Pusztai L, McArthur H, Kummel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. doi: 10.1056/NEJMoa1910549.

    PubMed 32101663

  • Chu DT, Bac ND, Nguyen KH, Tien NLB, Thanh VV, Nga VT, Ngoc VTN, Anh Dao DT, Hoan LN, Hung NP, Trung Thu NT, Pham VH, Vu LN, Pham TAV, Thimiri Govinda Raj DB. An Update on Anti-CD137 Antibodies in Immunotherapies for Cancer. Int J Mol Sci. 2019 Apr 12;20(8):1822. doi: 10.3390/ijms20081822.

    PubMed 31013788

  • Ye L, Jia K, Wang L, Li W, Chen B, Liu Y, Wang H, Zhao S, He Y, Zhou C. CD137, an attractive candidate for the immunotherapy of lung cancer. Cancer Sci. 2020 May;111(5):1461-1467. doi: 10.1111/cas.14354. Epub 2020 Apr 3.

    PubMed 32073704

  • Makkouk A, Chester C, Kohrt HE. Rationale for anti-CD137 cancer immunotherapy. Eur J Cancer. 2016 Feb;54:112-119. doi: 10.1016/j.ejca.2015.09.026. Epub 2016 Jan 2.

    PubMed 26751393

  • Qian Y, Pei D, Cheng T, Wu C, Pu X, Chen X, Liu Y, Shen H, Zhang W, Shu Y. CD137 ligand-mediated reverse signaling inhibits proliferation and induces apoptosis in non-small cell lung cancer. Med Oncol. 2015 Mar;32(3):44. doi: 10.1007/s12032-015-0499-9. Epub 2015 Jan 29.

    PubMed 25631633

  • Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA; National Comprehensive Cancer Network. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018 Jun 10;36(17):1714-1768. doi: 10.1200/JCO.2017.77.6385. Epub 2018 Feb 14.

    PubMed 29442540

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ADG106, Doxorubicin and Cyclophosphamide in people with HER2-negative Breast Cancer and Advanced Solid Tumor, run by National University Hospital, Singapore at 1 site in Singapore.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 25 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participant with treatment related toxicities (time frame: From enrolment till 30 days after last dose of study treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05275777, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in