Olaptesed With Pembrolizumab and Nanoliposomal Irinotecan or Gemcitabine/Nab-Paclitaxel in MSS Pancreatic Cancer (OPTIMUS)

• ClinicalTrials.gov Identifier: NCT04901741
• Recruitment Status: Not yet recruiting
• First Posted: May 25, 2021
• Last Update Posted: February 1, 2024
• Sponsor: TME Pharma AG
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): TME Pharma AG

Tracking Information

• First Submitted Date: May 20, 2021
• First Posted Date: May 25, 2021
• Last Update Posted Date: February 1, 2024
• Estimated Study Start Date: June 2024
• Estimated Primary Completion Date: October 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 20, 2021)

Go/no-go decision for a randomized expansion study [ Time Frame: until progression or intolerable toxicity to completion of 35 administrations (approximately 2 years) with pembrolizumab ]

Assessment of the disease control rate (DCR) at 6 weeks for the combination of olaptesed pegol on top of pembrolizumab and (Arm 1) nanoliposomal irinotecan, 5-FU and leucovorin or (Arm 2) gemcitabine and nab-paclitaxel

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 20, 2021)

• Safety and tolerability [ Time Frame: until progression or intolerable toxicity to completion of 35 administrations (approximately 2 years) with pembrolizumab ]
  Safety and tolerability of olaptesed pegol pegol on top of pembrolizumab and (Arm 1) nanoliposomal irinotecan, 5-FU and leucovorin or (Arm 2) gemcitabine and nab-paclitaxel
• DCR at 12 weeks [ Time Frame: until progression or intolerable toxicity to completion of 35 administrations (approximately 2 years) with pembrolizumab ]
• Progression free survival (PFS) [ Time Frame: until progression or intolerable toxicity to completion of 35 administrations (approximately 2 years) with pembrolizumab ]
• Overall response rate (ORR) [ Time Frame: until progression or intolerable toxicity to completion of 35 administrations (approximately 2 years) with pembrolizumab ]
• median Overall survival (mOS) [ Time Frame: until progression or intolerable toxicity to completion of 35 administrations (approximately 2 years) with pembrolizumab ]
• Duration of response (DOR) [ Time Frame: until progression or intolerable toxicity to completion of 35 administrations (approximately 2 years) with pembrolizumab ]
• Time-to-best overall response (TBOR) [ Time Frame: until progression or intolerable toxicity to completion of 35 administrations (approximately 2 years) with pembrolizumab ]
• Time-to-next-anticancer-treatment (TTNT) [ Time Frame: until progression or intolerable toxicity to completion of 35 administrations (approximately 2 years) with pembrolizumab ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Olaptesed With Pembrolizumab and Nanoliposomal Irinotecan or Gemcitabine/Nab-Paclitaxel in MSS Pancreatic Cancer
• Official Title: An Open-label Phase 2 Study of Olaptesed Pegol (NOX-A12) Combined With Pembrolizumab and Nanoliposomal Irinotecan/5-FU/Leucovorin or Gemcitabine/Nab-paclitaxel in Microsatellite-stable Metastatic Pancreatic Cancer Patients
• Brief Summary: The purpose of this study is to provide a go/no-go decision for a randomized expansion study by assessing the disease control rate (DCR) at 6 weeks for the combination of olaptesed pegol on top of pembrolizumab and (Arm 1) nanoliposomal irinotecan, 5-FU and leucovorin or (Arm 2) gemcitabine and nab-paclitaxel, to assess safety and tolerability and time-to-event endpoints.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Metastatic Pancreatic Cancer

Intervention

• Drug: Olaptesed pegol
  400 mg per week as continous infusion until progression or intolerable toxicity
  Other Name: NOX-A12
• Drug: Pembrolizumab
  200 mg every 3 weeks as i.v. infusion until progression or intolerable toxicity or a maximum of 35 administrations
  Other Name: KEYTRUDA®

Study Arms

• Experimental: Arm 1: olaptesed pegol + pembrolizumab + nanoliposomal irinotecan + 5-FU + LV
  Interventions:

  • Drug: Olaptesed pegol
  • Drug: Pembrolizumab
• Experimental: Arm 2: olaptesed pegol + pembrolizumab + gemcitabine + nab-paclitaxel
  Interventions:

  • Drug: Olaptesed pegol
  • Drug: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: August 24, 2023): 60
• Original Estimated Enrollment (submitted: May 20, 2021): 68
• Estimated Study Completion Date: October 2027
• Estimated Primary Completion Date: October 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patient with confirmed microsatellite-stable tumor pathology, if data available

• Patient with histologically or cytologically confirmed primary metastatic adenocarcinoma of the pancreas, who

  1. Arm 1: stopped first-line treatment with gemcitabine/nab-paclitaxel after documented objective radiographic progression OR
  2. Arm 2: stopped first-line treatment with FOLFIRINOX or modified FOLFIRINOX after documented objective radiographic progression
• Measurable disease based on RECIST 1.1 as determined by the investigational site
• Estimated minimum life expectancy 3 months
• Eastern Cooperative Oncology Group (ECOG) performance score 0 to 1
• Adequate organ function laboratory values within the ranges specified: Serum albumin ≥ 3.0 g/dL; Hematological system: Hemoglobin (Hb) ≥ 9.0 g/dL or ≥5.6 mmol/L, Absolute neutrophil count (ANC) ≥ 1,500/mm³, Platelets ≥ 100,000/mm³; Renal system: Creatinine ≤ 1.5 x ULN OR eGFR ≥30 mL/min for patient with creatinine levels >1.5 × institutional ULN; Hepatic system: Total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ULN for patients with total bilirubin levels >1.5 × ULN, ALT and AST ≤ 2.5 x ULN (≤5 × ULN for patients with liver metastases); Coagulation: INR OR PT ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants, aPTT ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

Exclusion Criteria:

• Prior systemic anti-cancer therapy including investigational agents within 4 weeks or 5 half-lives, whichever is shorter, prior to treatment.
• Patients must have recovered from all AEs due to previous therapies to ≤ Grade 1 or baseline. Patients with ≤ Grade 2 neuropathy may be eligible. Patients with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible.
• If the patient had major surgery, the patient must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention
• Prior radiotherapy within 2 weeks of start of study treatment. Patients must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137) and discontinued from that treatment due to a Grade 3 or higher irAE
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
• Received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention. Administration of killed vaccines are allowed
• Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• History of (non-infectious) pneumonitis / interstitial lung disease that required steroids or current pneumonitis / interstitial lung disease
• Active infection requiring systemic therapy
• Known additional malignancy that is progressing or has required active treatment within the past 2 years.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
• Previous allogeneic tissue/solid organ transplant

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Diana Beyer, Dr.; +49 30 72 62 47 ext 100; clinicaltrialdisclosuredesk@tmepharma.com

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04901741
• Other Study ID Numbers: SNOXA12C701; 2021-001963-25 ( EudraCT Number ); KEYNOTE-B01 ( Other Identifier: Merck Sharp & Dohme LLC ); MK-3475-B01 ( Other Identifier: Merck Sharp & Dohme LLC )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: TME Pharma AG
• Original Responsible Party: Same as current
• Current Study Sponsor: TME Pharma AG
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Not Provided
• PRS Account: TME Pharma AG
• Verification Date: January 2024