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Locally Advanced Pancreatic AdenocarcinomaPhase 1NCT05034627

Calaspargase Pegol-Mnkl and Cobimetinib for the Treatment of Locally Advanced or Metastatic Pancreatic Cancer

A Phase 1 study testing Biopsy, Calaspargase Pegol-mknl and Cobimetinib in people with Locally Advanced Pancreatic Adenocarcinoma and Metastatic Pancreatic Adenocarcinoma, run by OHSU Knight Cancer Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial tests the safety, side effects, and best dose of calaspargase pegol-mknl in combination with cobimetinib in treating patients with pancreatic cancer that has spread to nearby tissue or lymph nodes (locally advanced) or has spread to other places in the body (metastatic). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy, Calaspargase Pegol-mknl and Cobimetinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
1 siteUnited States
Study dates
9 Aug 2022to 3 Jun 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participant must provide written informed consent before any study-specific procedures or interventions are performed
  • Participants are >= 18 years old at the time of informed consent. Both men and women of all races and ethnic groups will be included
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Histologically or cytologically-proven adenocarcinoma of the exocrine pancreas with locally advanced or metastatic disease
  • Must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
  • Must have at least one disease lesion that is amenable to biopsy procedures performed per institutional standards
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  • Must have progressed on, been intolerant to, or refused systemic therapy that is consistent with institutional standards (e.g., Gemcitabine-based, or fluorouracil, irinotecan, leucovorin and oxaliplatin [FOLFORINOX])
  • Must not have received any systemic therapy or other investigational agents within 30 days or 5 half-lives (whichever is longer) from first dose of study therapy
  • This requirement is waived for patients receiving cobimetinib or other investigational agent(s) as part of participation in NCT04005690, provided that all prior study-drug-related toxicities pertaining to NCT04005690 have resolved to grade =< 1 prior to initiating study intervention
  • Hemoglobin: >= 8.5 g/dL with no blood transfusion within 14 days of starting treatment
  • White blood cells (WBC): > 2.5 x 10^9/L
  • Absolute neutrophil count (ANC): >= 1.2 x 10^9/L (> 1200 per mm^3)
  • Platelet count: >= 90 x 10^9/L (> 90,000 per mm^3)
  • Creatinine =< 1.5 x upper limit of normal (ULN), or measured or calculated creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels > 1 x institutional (ULN)
  • Serum bilirubin: =< 1.5 x institutional ULN
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT): =< 2.5 x ULN
  • Participants must be able to take anticoagulant therapy while receiving calaspargase pegol-mknl
  • Participants of childbearing potential (POCBP) must agree to abstain from sexual intercourse or use effective non-hormonal methods of contraception starting with the first dose of study therapy through 90 days after the last dose of study therapy (because calaspargase pegol can render hormonal contraceptives ineffective)
  • POCBP may participate provided they have a negative serum pregnancy test at screening and a negative serum OR urine pregnancy test within 7 days of starting treatment

Who cannot join

  • Concomitant use of other anti-cancer therapy (chemotherapy, immunotherapy, hormonal therapy (hormone replacement therapy is acceptable), radiotherapy (except for palliative), biological therapy or other novel agent) or live virus and live bacterial vaccines while receiving study medication
  • Prior treatment with an L-asparaginase therapy
  • Known severe hypersensitivity to calaspargase pegol-mknl (or equivalent) or to cobimetinib (or equivalent), or to any excipient of these medicinal products, or history of allergic reactions attributed to compounds of similar chemical or biologic composition to calaspargase pego-mknl or cobimetinib
  • Use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir), known strong CYP3A inducers (e.g., phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil) within 7 days of prior to initiating study treatment or on going requirement for these medications
  • Uncontrolled serious thrombosis
  • Uncontrolled severe or symptomatic coagulopathy; exclude if:
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  • Prothrombin time (PT) >= 1.5 x ULN, or
  • International normalized ratio (INR) >= 1.5 x ULN, or
  • Fibrinogen =< 0.66 x LLN
  • Known history of chronic pancreatitis or recurrent acute pancreatitis, or at time of screening evidence of acute pancreatitis, defined by at least two of the following:
  • Clinical symptoms of upper abdominal pain
  • Serum amylase or lipase that is >= 3 x ULN
  • Imaging evidence (computed tomography [CT], magnetic resonance imaging [MRI], ultrasonography)
  • Significant cardiac disease within 6 months prior to start of study treatment, including any of the following:
  • New York Heart Association class III or IV,
  • Congestive heart failure, acute coronary syndrome, and/or stroke, or
  • Left ventricular ejection fraction (LVEF) < 40% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan obtained within 28 days prior to start of study treatment
  • Known risk factors for ocular toxicity, consisting of any of the following:
  • History of serous retinopathy
  • History of retinal vein occlusion (RVO)
  • Evidence of ongoing serous retinopathy or RVO at screening
  • Uncontrolled hypertension, or hypertension that cannot otherwise be clinically managed before initiating study therapy
  • Participant is known to have dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
  • Participant has active uncontrolled systemic fungal, bacterial, or viral infection (defined as ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics, antiviral therapy, and/or other treatment)
  • Participant has corrected QT (QTc) interval (i.e., Fridericia's correction [QTcF]) >= 450 ms or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) at screening
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Any concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, etc.)
  • Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 90 days after the last dose of trial treatment
  • Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements

Trial locations and contacts

1 site in 1 country.

United States1 site

  • OHSU Knight Cancer Institute

    Portland, Oregon, 97239

Other trials in United States

About this study

Official title: A Phase I, Open-Label, Dose Finding Study of Calaspargase Pegol-Mnkl in Combination With Cobimetinib in Locally-Advanced or Metastatic Pancreatic Cancer

This phase I trial tests the safety, side effects, and best dose of calaspargase pegol-mknl in combination with cobimetinib in treating patients with pancreatic cancer that has spread to nearby tissue or lymph nodes (locally advanced) or has spread to other places in the body (metastatic). Cobimetinib attacks a protein called MEK that has been known to stimulate cells that promote the growth of cancer cells in the body. Calaspargase pegol-mknl is an enzyme that converts the amino acid L-asparagine into aspartic acid and ammonia. Many types of cancer cell rely on the amino acid L-asparagine, and depleting this amino acid with calaspargase pegol-mknl starves cancer cells of this nutrient. Attacking the MEK protein with cobimetinib is thought to further prevent cancer cells from using this amino acid, causing them to die. Giving calaspargase pegol-mknl in combination with cobimetinib may help control the disease in patients with pancreatic cancer.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the maximum tolerated dose (MTD) of calaspargase pegol-mknl in combination with cobimetinib.

SECONDARY OBJECTIVES:

  1. To assess the safety of calaspargase pegol-mknl in combination with cobimetinib.

II. To assess preliminary response to treatment with calaspargase pegol-mknl and cobimetinib.

III. To monitor levels of plasma asparaginase.

EXPLORATORY OBJECTIVE:

  1. To evaluate therapy induced changes in the tumor and tumor ecosystem.

OUTLINE: This is a dose-escalation study.

Patients receive calaspargase pegol-mknl intravenously (IV) over 1 hour on day 1 and cobimetinib orally (PO) once daily (QD) on days 1-14. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo a biopsy before cycle 1, day1 and again on cycle 2 day 15 per the investiagator's discretion, with an additional biopsy at the time of disease progression.

After completion of study intervention, patients are followed up at 3 and 6 months.

Being tested
Biopsy, Calaspargase Pegol-mknl, Cobimetinib
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo biopsy

  • Calaspargase Pegol-mknlDrug

    Also called Asparaginase (Escherichia coli Isoenzyme II), Conjugate with alpha-(((2,5-Dioxo-1-pyrrolidinyl)oxy)carbonyl)-omega-methoxypoly(oxy-1,2-ethanediyl), Asparlas, Calaspargase Pegol, EZN-2285

    Given IV

  • CobimetinibDrug

    Also called Cotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518

    Given PO

Study groups in NCT05034627
Study groupRoleWhat they receive
Treatment (calaspargase pegol-mknl, cobimetinib)ExperimentalPatients receive calaspargase pegol-mknl IV over 1 hour on day 1 and cobimetinib PO QD on days 1-14. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo a biopsy 14 days prior to starting therapybefore cycle 1, day 1 and again on day 14 of cycle 2, day 15 per the investigator's discretion, with an additional optional biopsy at the time of disease progression.
Receives: Procedure: Biopsy; Drug: Calaspargase Pegol-mknl; Drug: Cobimetinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of dose-limiting toxicities (DLTs)

    Defined as any treatment-related grade >= 3 non-hematological or hematological adverse events. The incidence of DLT at each dose level will be summarized using the proportion and exact binomial confidence interval. Dose-limiting toxicities will specifically be reported for the DLT evaluation period using the maximum tolerated dose (MTD)-evaluable population. The MTD will be identified using isotonic regression.

    Measured: Up to cycle 2 day 21 (1 cycle = 21 days)

Secondary outcomes (4)

  1. Incidence of treatment-emergent adverse events (AEs) and serious AEs

    Evaluated by Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 30 days after last dose of study intervention

  2. Objective response rate (ORR)

    Evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Overall response will be summarized descriptively. ORR will be estimated with 95% confidence interval. The confidence interval will be calculated based on the exact method for binomial distributions.

    Measured: Up to 6 months after initiating study intervention

  3. Disease control rate (DCR)

    Evaluated using RECIST version 1.1. An estimate of DCR will be measured and reported with 95% exact confidence interval. Participants who achieve a complete response, partial response, or stable disease for at least 6 months on the current protocol will be qualified as deriving benefit from therapy and will count towards the DCR measurement.

    Measured: Up to 6 months after initiating study intervention

  4. Mean plasma asparaginase activity

    Will be reported with 95% confidence interval.

    Measured: Up to 6 cycles from initiating study intervention (1 cycle = 21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Sep 2021
  2. Study start9 Aug 2022
  3. Primary completion7 Oct 2025
  4. Study completion3 Jun 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05034627
Sponsor's protocol ID
STUDY00022141
Other IDs
NCI-2021-09061, STUDY00022141
Status last verified
Jul 2026
First submitted
30 Aug 2021
Last updated
23 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Biopsy, Calaspargase Pegol-mknl and Cobimetinib in people with Locally Advanced Pancreatic Adenocarcinoma and Metastatic Pancreatic Adenocarcinoma, run by OHSU Knight Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose-limiting toxicities (DLTs) (time frame: Up to cycle 2 day 21 (1 cycle = 21 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05034627.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2026; AzTrials last refreshed its copy on 8 Nov 2026.

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