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

NCT05275777 | Active Not Recruiting Phase 1

• 1 other identifier: ADG106-T6002
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief 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. Primary Objectives

• 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.

Conditions

HER2-negative Breast Cancer; Advanced Solid Tumor

Keywords

HER2-negative Breast Cancer; ADG106; neoadjuvant doxorubicin and cyclophosphamide; paclitaxel

Outcome Measures

Primary Outcomes (2)

• 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.

  From enrolment till 30 days after last dose of study treatment

• Histological response after neoadjuvant ADG106 + chemotherapy

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

  After 20 weeks of neoadjuvant chemotherapy

Secondary Outcomes (7)

• Objective response rate in Phase Ib

  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)

• Overall survival in Phase Ib

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

• Correlation of plasma biomarkers with efficacy outcome in Phase Ib

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

• Progression free survival in Phase Ib

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

• Clinical response rate in Phase II

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

Study Arms (3)

ADG106 combined with dose dense Doxorubicin and Cyclophosphamide (Phase Ib)

EXPERIMENTAL

Intravenous ADG106 + 2 weekly doxorubicin and cyclophosphamide

Drug: ADG106; Drug: Doxorubicin; Drug: Cyclophosphamide

ADG106 combined with Paclitaxel (Phase Ib)

EXPERIMENTAL

Intravenous ADG106 + weekly paclitaxel

Drug: ADG106; Drug: Paclitaxel

ADG106 combined with dose dense Doxorubicin and Cyclophosphamide follow by Paclitaxel (Phase II)

EXPERIMENTAL

Intravenous ADG106 combined with two weekly doxorubicin and cyclophosphamide followed intravenous ADG106 combined with weekly paclitaxel

Drug: ADG106; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Paclitaxel

Interventions

ADG106 DRUG

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

ADG106 combined with Paclitaxel (Phase Ib); ADG106 combined with dose dense Doxorubicin and Cyclophosphamide (Phase Ib); ADG106 combined with dose dense Doxorubicin and Cyclophosphamide follow by Paclitaxel (Phase II)

Doxorubicin DRUG

Administered as an intravenous infusion.

Also known as: Adriamycin

ADG106 combined with dose dense Doxorubicin and Cyclophosphamide (Phase Ib); ADG106 combined with dose dense Doxorubicin and Cyclophosphamide follow by Paclitaxel (Phase II)

Cyclophosphamide DRUG

Administered as an intravenous infusion.

Also known as: Cytophosphane

ADG106 combined with dose dense Doxorubicin and Cyclophosphamide (Phase Ib); ADG106 combined with dose dense Doxorubicin and Cyclophosphamide follow by Paclitaxel (Phase II)

Paclitaxel DRUG

Administered as an intravenous infusion.

Also known as: Taxol

ADG106 combined with Paclitaxel (Phase Ib); ADG106 combined with dose dense Doxorubicin and Cyclophosphamide follow by Paclitaxel (Phase II)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• National University Hospital, Singapore: lead
• Adagene Inc: collaborator

Study Sites (1)

National University Hospital

Singapore, Singapore

Location

Related Publications (10)

• 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.

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• 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.

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• 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.

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MeSH Terms

Interventions

Doxorubicin; Cyclophosphamide; Paclitaxel

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes

Study Officials

• Soo Chin Lee

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 9, 2022
• First Posted: March 11, 2022
• Study Start: May 19, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): February 1, 2030
• Last Updated: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)