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

NCT05034627 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: STUDY00022141NCI-2021-09061
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Locally Advanced Pancreatic Adenocarcinoma; Metastatic Pancreatic Adenocarcinoma; Stage II Pancreatic Cancer AJCC v8; Stage IIA Pancreatic Cancer AJCC v8; Stage IIB Pancreatic Cancer AJCC v8; Stage III Pancreatic Cancer AJCC v8; Stage IV Pancreatic Cancer AJCC v8

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (4)

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

  Up to 30 days after last dose of study intervention

• Objective response rate (ORR)

  Up to 6 months after initiating study intervention

• Disease control rate (DCR)

  Up to 6 months after initiating study intervention

• Mean plasma asparaginase activity

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

Other Outcomes (1)

• Therapy induced changes in the tumor and tumor ecosystem

  Up to 6 cycles from completing study intervention (1 cycle = 21 days)

Study Arms (1)

Treatment (calaspargase pegol-mknl, cobimetinib)

EXPERIMENTAL

Patients 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.

Procedure: Biopsy; Drug: Calaspargase Pegol-mknl; Drug: Cobimetinib

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (calaspargase pegol-mknl, cobimetinib)

Calaspargase Pegol-mknl DRUG

Given IV

Also known as: 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, SC-PEG E. Coli L-Asparaginase, Succinimidyl Carbonate Monomethoxypolyethylene Glycol E. coli L-Asparaginase

Treatment (calaspargase pegol-mknl, cobimetinib)

Cobimetinib DRUG

Given PO

Also known as: Cotellic, GDC-0973, MEK Inhibitor GDC-0973, XL518

Treatment (calaspargase pegol-mknl, cobimetinib)

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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:
• 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,

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator
• Genentech, Inc.: collaborator
• Servier Pharmaceuticals, LLC: collaborator

Study Sites (1)

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Biopsy; calaspargase pegol; Asparaginase; cobimetinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes

Study Officials

• Charles D Lopez

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 30, 2021
• First Posted: September 5, 2021
• Study Start: August 9, 2022
• Primary Completion: December 16, 2025
• Study Completion (Estimated): October 1, 2026
• Last Updated: November 28, 2025

Record last verified: 2025-11

Locations

US (1)