Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Anti-Infective Agents

Paclitaxel

Albumin-Bound Paclitaxel

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Tubulin Modulators

Antimitotic Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Intravenous ADG106 + 2 weekly doxorubicin and cyclophosphamide

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

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

ADG106

Soo Chin Lee

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.

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

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.

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 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

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

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

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

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.

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

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

Clinical response rate will be measured by calipers

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.

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

Spots Global Cancer Trial Database for neoadjuvant doxorubicin and cyclophosphamide