Testing the Combination of Anti-Cancer Drugs, Selumetinib and DS-8201a, for Advanced Pancreatic Ductal Adenocarcinoma

NCT07619521 | Not Yet Recruiting Phase 1 FDA Drug

• 3 other identifiers: NCI-2026-0386810733UM1CA186689
• Study Type: interventional
• Target: 31
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase I/II trial tests the safety, side effects, best dose and how well giving selumetinib with DS-8201a works for the treatment of pancreatic ductal adenocarcinoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced), that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic). Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. DS-8201a is in a class of medications called antibody-drug conjugates. It is composed of 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. Giving selumetinib with DS-8201a may be safe, tolerable and/or effective in treating patients with advanced, unresectable or metastatic pancreatic ductal adenocarcinoma.

Conditions

Unresectable Pancreatic Ductal Adenocarcinoma; Advanced Pancreatic Ductal Adenocarcinoma; Metastatic Pancreatic Ductal Adenocarcinoma; Stage III Pancreatic Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8

Outcome Measures

Primary Outcomes (3)

• Occurrence of dose limiting toxicities (DLTs) (dose escalation phase)

  Will provide the number and proportion of DLTs provide and 95% confidence intervals.

  From baseline up to day 21

• HER2 expression status (dose escalation phase)

  Will be evaluated descriptively during the dose escalation phase with respect to safety, tolerability and preliminary antitumor activity.

  Up to 1 year

• Overall response rate (phase II)

  Defined as confirmed responses by Response Evaluation Criteria in Solid Tumors version (v) 1.1. A confirmed response requires documentation of a complete response (CR) or partial response (PR) on a subsequent imaging assessment performed at least ≥ 4 weeks after the initial response is observed.

  Up to 1 year

Secondary Outcomes (8)

• Incidence of adverse events

  Up to 1 year

• Biochemical response

  Up to 1 year

• Time to response

  From the first dose of study treatment to the first documentation of a confirmed objective response, up to 1 year

• Duration of response

  From the first documentation of confirmed objective response (CR or PR) to the date of first documented disease progression or death, up to 1 year

• Disease control rate

  Up to 1 year

Other Outcomes (5)

• Selumetinib (AZD6244 hydrogen sulfate) pharmacokinetics (PK)

  Cycle 1 day 1 pre-dose, at 0.5, 1, 2, 3, 4, and 8 hours post dose and at cycle 1 day 1 pre-dose (cycle length = 21 days)

• Immunogenicity

  At cycle 1 day 1 pre-dose, pre-dose at day 1 of cycles 2, 4 and 8 and at progression (phase II only) (cycle length = 21 days)

• PK parameters

  Up to 1 year

Study Arms (1)

Treatment (Selumetinib and DS-8201a)

EXPERIMENTAL

Patients receive selumetinib PO BID on days 1-21 of each cycle and DS-8201a IV, over 30-90 minutes, on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography or MUGA scan, diagnostic imaging and blood sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Diagnostic Imaging Testing; Procedure: Echocardiography Test; Procedure: Multigated Acquisition Scan; Drug: Selumetinib; Biological: Trastuzumab Deruxtecan

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (Selumetinib and DS-8201a)

Diagnostic Imaging Testing PROCEDURE

Undergo diagnostic imaging

Also known as: Diagnostic Imaging, Medical Imaging

Treatment (Selumetinib and DS-8201a)

Echocardiography Test PROCEDURE

Undergo echocardiography

Also known as: EC, Echocardiography

Treatment (Selumetinib and DS-8201a)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA scan

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (Selumetinib and DS-8201a)

Selumetinib DRUG

Given PO

Also known as: ARRY-142886, AZD 6244, AZD-6244, AZD6244, MEK Inhibitor AZD6244

Treatment (Selumetinib and DS-8201a)

Trastuzumab Deruxtecan BIOLOGICAL

Given IV

Also known as: DS-8201, DS-8201a, Enhertu, Fam-trastuzumab Deruxtecan-nxki, T-DXd, WHO 10516

Treatment (Selumetinib and DS-8201a)

Eligibility Criteria

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

You may qualify if:

• Review of eligibility criteria by the study principal investigator (PI) is required prior to enrollment
• Patients must have histologically or cytologically confirmed adenocarcinoma of the pancreas
• Patients must have unresectable or metastatic disease with KRAS mutation per Next Generation Sequencing (NGS) tumor testing and HER2 immunohistochemistry (IHC) positivity (2+ or above for dose escalation and per decision rule for phase II), as determined by a Clinical Laboratory Improvement Act (CLIA)-certified kit using gastric cancer criteria
• Patients must have measurable disease that can fulfill Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
• Patients must have exposure to at least one line of systemic chemotherapy for metastatic or unresectable PDAC (for both escalation and phase II cohorts) or a documented patient decision to forego therapy that has an otherwise proven survival advantage (for escalation cohort only)
• Patients who have received prior topoisomerase inhibitors including irinotecan and nanoliposomal irinotecan will be eligible for this study
• Only 1 prior line of therapy for metastatic or unresectable PDAC will be allowed for patients in the phase II cohort. Adjuvant or neoadjuvant therapy does not count, assuming it was completed \> 6 months prior to the start of systemic therapy for metastatic or unresectable disease
• Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of selumetinib (AZD6244 hydrogen sulfate) in combination with DS-8201a in patients \< 18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 70%). Regardless of performance status, enrollment should be based on the judgment of the treating physician that the patient will be able to be safely treated with the proposed therapeutic intervention
• Hemoglobin ≥ 9 g/dL (within 14 days of enrollment)
• No transfusions with red blood cells or platelets are allowed within 1 week prior to screening assessment
• Leukocytes ≥ 3,000/mcL (within 14 days of enrollment)
• Absolute neutrophil count ≥ 1,500/mcL (within 14 days of enrollment)
• No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 1 week prior to screening assessment
• Platelets ≥ 100,000/mcL (within 14 days of enrollment)

You may not qualify if:

• Patients with prior MEK inhibitor, ERK inhibitor, or HER2-directed therapy treatment
• Patients who have had chemotherapy (including antibody drug therapy, retinoid therapy, hormonal therapy for cancer) within 3 weeks (2 weeks or five half-lives, whichever is longer for small-molecule targeted agents such as 5-fluorouracil-based agents, folinate agents), weekly paclitaxel; 6 weeks for nitrosoureas or mitomycin C
• Patients who have had immunotherapy including monoclonal antibody therapy within 4 weeks
• Patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies
• Patients who have had a major surgery within 4 weeks
• Patients with a history of allogeneic organ or stem cell transplant
• Patients who are receiving any other investigational agents or received any other investigational agents within the past 21 days prior to protocol treatment initiation
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to selumetinib (ADZ6244 hydrogen sulfate) or DS-8201a
• Current use or anticipated need for alternative, holistic, naturopathic, or botanical formulations used for the purpose of cancer treatment
• Patients with prior use of immunosuppressive medication within 14 days prior to first study dose, except for intranasal and inhaled corticosteroids or systemic corticosteroids at doses less than 10 mg/day of prednisone or equivalent
• Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
• Patients with a corrected QT interval (QTc) prolongation to \> 470 ms (females) or \> 450 ms (males) based on average of the screening triplicate 12-lead electrocardiogram (ECG)
• Patients with a history of (non-infectious) interstitial lung disease (ILD) that required steroids, presence of ILD that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity, or where suspected ILD cannot be ruled out by imaging at screening. These patients will be excluded because DS-8201a is known to increase the risk of developing ILD and pneumonitis
• Patients with lung-specific, intercurrent, clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months prior to study enrollment, severe asthma, severe chronic obstructive pulmonary disorder (COPD), restrictive lung disease, significant pleural effusion, etc.), and any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (i.e., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), and/or prior pneumonectomy. These patients will be excluded because DS-8201a is known to increase the risk of developing ILD and pneumonitis
• Patients with gastrointestinal conditions which could impair absorption of selumetinib (AZD6244 hydrogen sulfate) or inability to ingest selumetinib (AZD6244 hydrogen sulfate)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Specimen Handling; X-Rays; AZD 6244; trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing

Study Officials

• Anup K Kasi Loknath Kumar

  Yale University Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2026
• First Posted: June 2, 2026
• Study Start (Estimated): September 8, 2026
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): October 30, 2026
• Last Updated: June 11, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share