Ph1b/2 Study of the Safety and Efficacy of T-DXd Combinations in Advanced HER2-expressing Gastric Cancer (DESTINY-Gastric03)
A Phase 1b/2 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of Trastuzumab Deruxtecan (T-DXd) Monotherapy and Combinations in Adult Participants With HER2-expressing Gastric Cancer (DESTINY-Gastric-03)
AstraZeneca
450 participants
Jun 3, 2020
INTERVENTIONAL
Conditions
Summary
DESTINY-Gastric03 will investigate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumor activity of trastuzumab deruxtecan (T-DXd) alone or in combination with chemotherapy and/or immunotherapy in HER2-expressing advanced/metastatic gastric/gastroesophageal junction (GEJ) and esophageal adenocarcinoma patients. Study hypotheses: Combination of T-DXd with cytotoxic chemotherapy and/or immunotherapy administered to subjects at the recommended phase 2 dose will show manageable safety and tolerability and preliminary anti-tumor efficacy so as to permit further clinical testing. T-DXd in combination with cytotoxic chemotherapy or immune checkpoint inhibitor administered to HER2-expressing gastric, GEJ and esophageal cancer patients who have not received prior treatment for advanced/metastatic disease will show preliminary evidence of anti-tumour activity and the potential to become a therapeutic option for this patient population.
Eligibility
Inclusion Criteria9
- Male and female participants must be at least 18 years of age. Other age restrictions may apply as per local regulations
- Disease Characteristics:
- Locally advanced, unresectable, or metastatic disease based on most recent imaging
- For Part 1, 2, 3a, 4a pathologically documented adenocarcinoma of the stomach/GEJ/esophagus, HER2-positive (IHC 3+ or IHC 2+/ISH+) based on local tissue testing results
- For Part 3b,4b and Part 5, pathologically documented adenocarcinoma of the stomach/GEJ/esophagus, HER2-low (IHC 2+/ISH-negative or IHC 1+) based on local tissue testing results
- For Part 1, progression on or after at least one prior trastuzumabcontaining regimen For Part 2, Part 3, Part 4 and Part 5, previously untreated for unresectable or metastatic adenocarcinoma of the stomach/GEJ/ esophagus with with HER2-positive (Part 2 and Part 3 \[Arm 3A\] and Part 4 \[Arm 4A\]) or HER2-low (Part 3 \[Arm 3B\], Part 4 \[Arm 4B\] and Part 5)) status
- Has measurable target disease assessed by the Investigator based on RECIST version 1.1
- Has protocol defined adequate bone marrow and organ function including cardiac, renal and hepatic function
- If of reproductive potential, agrees to use a highly effective form of contraception or avoid intercourse during and upon completion of the study.
Exclusion Criteria7
- Part 1 to 4: History of active primary immunodeficiency, known HIV, active chronic, or past hepatitis B infection, or hepatitis C infection. Part 5: evidence of active, uncontroled HIV, HBV or HCV infection.
- Uncontrolled intercurrent illness.
- History of non-infectious pneumonitis/ILD, 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).
- Has spinal cord compression or clinically active central nervous system metastases.
Interventions
Oxaliplatin: administered as an IV infusion
Trastuzumab: administered as an IV infusion
T-DXd: administered as an IV infusion
Durvalumab: administered as an IV infusion
5-FU: administered as an IV infusion
Capecitabine: administered orally
Cisplatin: administered as an IV infusion
Pembrolizumab: administered as an IV infusion
Volrustomig: administered as an IV infusion
Rilvegostomig: administered as an IV infusion
Locations(100)
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NCT04379596