A Phase II, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of Trastuzumab Deruxtecan (T-DXd, DS-8201a) for the Treatment of Selected HER2-Expressing Tumors (DESTINY-PanTumor02)

ENROLLING
Protocol # :
21-051
Conditions
Part 1: Bladder, Biliary Tract, Cervical, Endometrial, Ovarian, Pancreatic Cancer, Rare Tumors, Any Tumor Type Excluding Breast, Gastric, Colorectal Cancer
Part 2: HER2 Expressing/Amplified Solid Tumors Excluding Breast, Gastric, Colorectal Cancer
Phase
II
Disease Sites
Healthy volunteer
Transplanted organ and tissue status, unspecified
Disease not specified
Neuroendocrine/Carcinoid
Gastroesophageal Junction
Gallbladder/Biliary
Other specified personal risk factors, not elsewhere classified
Lip, Oral Cavity and Pharynx
Esophagus
Anus
Liver
Pancreas
Larynx
Other Respiratory and Intrathoracic Organs
Bones and Joints
Soft Tissue
Mycosis Fungoides
Other Skin
Cervix
Corpus Uteri
Ovary
Other Female Genital
Prostate
Other Male Genital
Urinary Bladder
Kidney
Other Urinary
Eye and Orbit
Brain and Nervous System
Thyroid
Unknown Sites
Ill-Defined Sites
Other Endocrine System
Donors
Kaposi's Sarcoma
Melanoma, Skin
Principal Investigator
Konstantinopoulos, Panagiotis, A.
Site Research Nurses
Baylies, Rosemarie
Carey, Margaret, M.
Hart, Kayla
Hedglin, Jennifer
QUINN, NICHOLAS

Trial Description

This is an open-label, multi-center, multi-cohort, Phase 2 study to evaluate the efficacy and
safety of trastuzumab deruxtecan (T-DXd) for the treatment of selected HER2-expressing
tumors.

This study will consist of Part 1 which includes 7 cohorts of: urothelial bladder cancer,
biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer,
and rare tumors; and Part 2 which includes 5 cohorts A to E of: A) any tumor type that is
HER2 IHC 3+ (excluding breast, gastric cancer, and colorectal cancer), B) any tumor type that
is HER2 IHC 2+/ISH+ (excluding breast, gastric cancer, and colorectal cancer), C) HER2 IHC 2+
or 1+ endometrial cancer, D) HER2 IHC 2+ or 1+ ovarian cancer, and E) HER2 IHC 2+ or 1+
cervical cancer.

Study hypothesis: Trastuzumab deruxtecan will show meaningful clinical activity and a
favorable risk benefit profile in selected HER2-expressing solid tumors.

Eligibility Requirements

Inclusion Criteria:

- Locally advanced, unresectable, or metastatic disease based on most recent imaging.

- Part 1:The respective cohorts for patient inclusion are:

- Cohort 1: Biliary tract cancer

- Cohort 2: Bladder cancer

- Cohort 3: Cervical cancer

- Cohort 4: Endometrial cancer

- Cohort 5: Epithelial ovarian cancer

- Cohort 6: Pancreatic cancer

- Cohort 7: Rare tumors: This cohort will consist of patients with tumors that
express HER2, excluding the tumors mentioned above, and breast, non-small cell
lung cancer, gastric cancer, and colorectal cancer.

- Part 2:The respective cohorts for patient inclusion are:

- Cohort A: Metastatic or advanced solid tumors that are HER2 IHC 3+ (excluding
breast, gastric cancer, and colorectal cancer). Patients with non-small cell lung
cancer can be included.

- Cohort B: Metastatic or advanced solid tumors that are HER2 IHC 2+/ISH+ any tumor
type (excluding breast, gastric cancer, and colorectal cancer). Patients with
non-small cell lung cancer can be included.

- Cohort C: Metastatic or advanced solid endometrial cancer that is HER2 IHC 2+ or
1+.

- Cohort D: Metastatic or advanced ovarian cancer that is HER2 IHC 2+ or 1+.

- Cohort E: Metastatic or advanced solid cervical cancer that is HER2 IHC 2+ or 1+.

- Progressed following prior treatment or who have no satisfactory alternative treatment
option.

- Prior HER2 targeting therapy is permitted.

- HER2 expression scored using current ASCO/CAP guidelines for scoring HER2 for gastric
cancer.

- Part 1: IHC 3+ or IHC 2+ by local or central assessment

- Part 2: IHC and ISH results by central assessment as pre-defined for each cohort

- Has measurable target disease assessed by the Investigator based on RECIST version
1.1.

- Has protocol- defined adequate organ function including cardiac, renal and hepatic
function.

Exclusion Criteria:

- History of non-infectious pneumonitis/ILD that required steroids, current ILD, or
where suspected ILD that cannot be ruled out by imaging at screening

- Lung-specific intercurrent clinically significant severe illnesses

- Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or
antifungals

- Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal
shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART

- Known Somatic DNA mutation of HER2 (ERBB2) without tumoral HER2 protein expression.

- Primary diagnosis of adenocarcinoma of the breast, adenocarcinoma of the colon or
rectum, adenocarcinoma of the gastric body or gastro-esophageal junction, or non-small
cell lung cancer for Part 1. For Part 2, patients with primary diagnosis of
adenocarcinoma of the breast, adenocarcinoma of the colon or rectum, adenocarcinoma of
the gastric body or gastro-esophageal junction will be excluded.

- Medical conditions that may interfere with the subject's participation in the study.

21-051