Neoplasms

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Colonic Neoplasms

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Salivary Gland Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

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Gastrointestinal Diseases

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Genital Diseases

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Female Urogenital Diseases and Pregnancy Complications

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Mouth Diseases

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Salivary Gland Diseases

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Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

Trastuzumab deruxtecan

Camptothecin

Immunoconjugates

Antineoplastic Agents, Immunological

Immunologic Factors

Topoisomerase I Inhibitors

Enzyme Inhibitors

Patients receive trastuzumab deruxtecan IV over 30-90 minutes on day 1 and ceralasertib PO BID on days 1-7. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. NOTE: During the dose-expansion phase, the first 6 patients in each disease cohort (gastroesophageal cancer \[cohort A\] and colorectal cancer \[cohort B\]) receive only trastuzumab deruxtecan for the first cycle, followed by trastuzumab deruxtecan and ceralasertib together in subsequent cycles.

Ceralasertib

Trastuzumab Deruxtecan

Site Public Contact

Heinz-Josef Lenz

Farshid Dayyani

Jonathan W. Riess

Jibran Ahmed

Patrick Grierson

Despina Siolas

Susanna V. Ulahannan

Babar Bashir

Kyaw L. Aung

Syed M. Kazmi

Kanwal P. Raghav

Vaia Florou

Kanwal P Raghav

The dose escalation phase of this trial identifies the best dose and safety of ceralasertib (AZD6738) when given in combination with trastuzumab deruxtecan (DS-8201a) in treating patients with solid tumors that have a change (mutation) in the HER2 gene or protein and have spread to other places in the body (advanced). The dose expansion phase (phase Ib) of this trial compares how colorectal and gastroesophageal cancers with HER2 mutation respond to treatment with a combination of ceralasertib and trastuzumab deruxtecan versus trastuzumab deruxtecan alone. Trastuzumab deruxtecan is a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers deruxtecan to kill them. Ceralasertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. Evaluate safety, tolerability, and recommended phase 2 dose (RP2D) of trastuzumab deruxtecan (DS-8201a) in combination with ceralasertib (AZD6738) in advanced solid tumors with HER2 expression. (Escalation Phase) II. Assess differential pharmacodynamic (PD) profile of tumor tissue (deoxyribonucleic acid \[DNA\] damage \& repair) between Top1 inhibition and dual inhibition of Top1 and ATR in patients with colorectal cancer and gastroesophageal cancer with HER2 expression. (Expansion Phase)

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity. II. To evaluate pharmacokinetics (PK) of DS-8201a and AZD6738 and immunogenicity of DS8201a.

EXPLORATORY OBJECTIVES:

I. Evaluate association between HER2 heterogeneity and response to DS-8201a plus (+) AZD6738 therapy using central protein expression assessment.

II. Determine predictive biomarkers (including but not restricted to: HER2 protein levels, HER2 gene copy number, alterations of TP53, ATM and RAS) of DS-8201a + AZD6738 efficacy in advanced solid tumors (specifically colorectal cancer and gastroesophageal cancer) with HER2 expression.

III. To characterize PD biomarkers for efficacy of DS-8201a + AZD6738 efficacy in advanced solid tumors (specifically colorectal cancer and gastroesophageal cancer) with HER2 expression (such as phosphorylated \[p\]RAD50 and SLFN11).

IV. To establish a biorepository of tissue, blood and pre-clinical models (PDXs) for HER2 expressing advanced solid tumors (specifically colorectal cancer and gastroesophageal cancer).

OUTLINE: This is a dose-escalation study of ceralasertib with fixed dose trastuzumab deruxtecan followed by a dose-expansion study.

Patients receive trastuzumab deruxtecan intravenously (IV) over 30-90 minutes on day 1 and ceralasertib orally (PO) twice daily (BID) on days 1-7. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. NOTE: During the dose-expansion phase, the first 6 patients in each disease cohort (gastroesophageal cancer \[cohort A\] and colorectal cancer \[cohort B\]) receive only trastuzumab deruxtecan for the first cycle, followed by trastuzumab deruxtecan and ceralasertib together in subsequent cycles.

After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years.

Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Patients With Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial

Phase 1/1B Study of DS-8201a in Combination With ATR Inhibition (AZD6738) in Advanced Solid Tumors With HER2 Expression (DASH Trial)

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Chi-squared tests/Fisher-exact test will be used to study these associations.

The descriptions and grading scales found in the revised National Cancer institute Common Terminology Criteria for Adverse Events version 5.0 will be utilized for adverse event reporting.

Will be determined based on the totality of safety, clinical activity, and pharmacokinetic data.

Will assess differential PD profile of tumor tissue between Top1 inhibition and dual inhibition of Top1 and ATR.

Assessed by Response Evaluation Criteria in Solid Tumors 1.1 criteria.

For each cohort the ORR and its 95% exact confidence interval will be estimated using the Clopper and Pearson Method.

Will compare PD markers between the groups. Descriptive statistics will be used.

National Cancer Institute (NCI)

Reproductive Control Agents

Leuprolide

Antineoplastic Agents, Hormonal

This arm for HER2-alteration salivray gland carcinoma.

This arm for AR-postive salivray gland carcinoma.

This arm for salivray gland carcinoma without HER-2 alteration or AR-postive.

This arm for low HER2 expression salivray gland carcinoma.

SHR-A1811

SHR 3680 + leuprolide

SHR-A1921

Dongmei Ji, Doctor

Dongmei Ji

This is a single-center, open-label, phase 2 study to evaluate the efficacy and safety of target therapy for patients with relapsed/metastastic salivary gland carcinoma based on molecular typing.

Patients with IHC HER2 IHC 3+ or IHC 2+/ISH+ will be located into arm 1 to receive anti-her2 ADC（SHR- A1811） Patients with IHC AR positive will be located into arm 2 to receive anti-androgen therapy (SHR-3680)+leuprolide Patients with HER2 negative and AR negative will be located into arm 3 to receive anti-TROP2 ADC (SHR-A1921) Patients with IHC HER2 IHC 1+ or IHC 2+/ISH- will be located into arm 4 to receive anti-her2 ADC（SHR- A1811）

A Phase II Study of Advanced Salivary Gland Carcinoma Based on Molecular Typing

Objective response rate defined as the patients confirmed complete response or partial response under RECIST 1.0 criteria.

DCR defined as the patients confirmed complete response or partial response or stable disease under RECIST 1.0 criteria.

Progression-free Survival (PFS) (median) was determined using the number of months measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression) of participants. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Overall Survival (OS) (median) was determined using the number of months measured from the initial date of treatment to the recorded date of death of participants.

Hematologic and non hematologic adverse event (CTCAE 5.0）

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Testing the Combination of Two Anti-cancer Drugs, DS-8201a and AZD6738, for The Treatment of Patients With Advanced Solid Tumors Expressing the HER2 Protein or Gene, The DASH Trial	NCT04704661	Advanced Breast... Advanced Colon ... Advanced Colore... Advanced Endome... Advanced Gastri... Advanced Gastro... Advanced Malign... Advanced Saliva... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Anatomic Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... HER2-Positive B... Malignant Hepat... Metastatic Brea... Metastatic Gast... Metastatic Mali... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Prognostic Stag... Stage III Colon... Stage III Color... Stage III Major... Stage III Uteri... Stage IIIA Colo... Stage IIIA Colo... Stage IIIA Uter... Stage IIIB Colo... Stage IIIB Colo... Stage IIIB Uter... Stage IIIC Colo... Stage IIIC Colo... Stage IIIC Uter... Stage IIIC1 Ute... Stage IIIC2 Ute... Stage IV Colon ... Stage IV Colore... Stage IV Major ... Stage IV Uterin... Stage IVA Colon... Stage IVA Color... Stage IVA Major... Stage IVA Uteri... Stage IVB Colon... Stage IVB Color... Stage IVB Major... Stage IVB Uteri... Stage IVC Colon... Stage IVC Color... Stage IVC Major... Unresectable Co... Unresectable Ga... Unresectable Ma...	Ceralasertib Trastuzumab Der...	18 Years -	National Cancer Institute (NCI)
A Phase II Study of Advanced Salivary Gland Carcinoma Based on Molecular Typing	NCT05924256	Advanced Saliva...	SHR-A1811 SHR 3680 + leup... SHR-A1921 SHR-A1811	18 Years - 75 Years	Fudan University

Spots Global Cancer Trial Database for advanced salivary gland carcinoma