An open-label phase 1b/2 study assessing the safety and efficacy of mitazalimab in combination with chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Alligator Bioscience AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Sep 2021 → ongoing

Decision date (initial)

2024-10-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514905-79-00

EudraCT number

2020-005182-14

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Efficacy, Safety

Part 1: To determine the recommended Phase 2 dose (RP2D) of mitazalimab in combination with chemotherapy
Part 2 and 3: To assess the clinical activity of mitazalimab in combination with chemotherapy (i.e., anti-tumor activity as per RECIST v. 1.1 guideline)

Secondary objectives 5

1. 1. To assess the safety and tolerability of mitazalimab in combination with chemotherapy
2. 2. To assess the immunogenicity of mitazalimab
3. 3. To assess pharmacokinetics (PK) of mitazalimab after single and repeated administrations
4. 4. To assess the clinical activity of mitazalimab in combination with chemotherapy (i.e., anti-tumor activity as per RECIST v. 1.1 guideline)
5. 5. To assess survival outcomes following repeated administrations of mitazalimab in combination with chemotherapy

Conditions and MedDRA coding

Metastatic pancreatic ductal adenocarcinoma

Regulatory references

Scientific advice from competent authorities

Swedish Medical Products Agency

Plan to share IPD

Yes

IPD plan description

The results will be posted on clinicaltrials.gov and in a peer-reviewed journal.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. 1. Has provided written informed consent
2. 2. Is ≥18 years of age at the time of signing the informed consent form (ICF)
3. 3. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. 4. Has a diagnosis of previously untreated metastatic pancreatic ductal adenocarcinoma (histologically documented)
5. 5. Has measurable disease per RECIST v. 1.1
6. 6. Has not received previous chemotherapy for pancreatic ductal adenocarcinoma
7. 7. Has not received prior abdominal radiotherapy (except for palliative radiotherapy to non-target lesions)
8. 8. Has a life expectancy of ≥ 3 months
9. 9. Has acceptable hematologic laboratory values defined as: a. Neutrophils ≥ 1.5 x 109/L without growth factor stimulation within 3 weeks prior to the blood test b. Platelets ≥100 x 109/L c. Hemoglobin ≥6.2 mmol/L (~100 g/L) (may be after transfusion)
10. 10. Has acceptable clinical chemistry laboratory values defined as: a. Bilirubin ≤1.5 x ULN (biliary drainage is permitted) b. AST ≤3 x ULN (irrespective of hepatic metastases) c. ALT ≤3 x ULN (irrespective of hepatic metastases) d. Creatinine ≤1.5 x ULN or glomerular filtration rate (GFR) of ≥45 mL/min (see APPENDIX 4 for calculation of GFR) e. INR ≤1.5 x ULN f. Albumin ≥28 g/L
11. 11. For women of childbearing potential: a. Has a negative highly sensitive serum (β-human chorionic gonadotropin [β-hCG]) pregnancy test at screening b. Is willing to use highly effective contraception methods (defined in APPENDIX 5) during study treatment and for at least six months thereafter
12. 12. Fertile men must practice effective contraceptive methods (i.e. surgical sterilization, or a condom used with a spermicide) during study treatment and for at least six months thereafter
13. 13. Is willing to comply with all study procedures

Exclusion criteria 22

1. 1. Has other types of non-ductal tumor of the pancreas, including endocrine tumors or acinar cell adenocarcinoma, cyst adenocarcinoma and ampullary carcinoma
2. 2. Has other current cancer or history of cancer in the prior 3 years before signing the ICF other than in situ cervical cancer, or basal cell or squamous cell carcinoma treated with local excision only
3. 3. Has known CNS metastases or carcinomatous meningitis
4. 4. Has contraindication to any constituent of study treatment (mitazalimab and applicable chemotherapy)
5. 5. Has a history of chronic diarrhea, inflammatory disease of the colon or rectum, or unresolved partial or complete intestinal obstruction
6. 6. Has a history of myocardial infarction within 12 months of the first administration of mitazalimab, uncontrolled angina pectoris, unstable cardiac arrhythmias, or congestive heart failure of New York Heart Association class II or greater
7. 7. Has QTc >450 msec
8. 8. Has uncontrolled intercurrent illness, including active infection
9. 9. Has a known history of HIV, hepatitis B or active hepatitis C infection
10. 10. Is a female patient who is pregnant or nursing
11. 11. Has received attenuated vaccine within 28 days before the first dose of study treatment
12. 12. Any condition that, in the opinion of the Investigator, would place the patient at increased risk or preclude the patient’s compliance with the study
13. 13. Participates in another investigational drug or device study with any intervention within the previous 4 weeks prior to first dose of mitazalimab
14. 14. Additional exclusion criteria only applicable for mFOLFIRINOX treatment: Has received prior treatment with irinotecan or platinum-containing chemotherapy
15. 15. Additional exclusion criteria only applicable for mFOLFIRINOX treatment: Has pre-existing peripheral neuropathy greater than grade 1
16. 16. Additional exclusion criteria only applicable for mFOLFIRINOX treatment: Has known Gilbert's disease
17. 17. Additional exclusion criteria only applicable for mFOLFIRINOX treatment: Has known genotype UGT1A1 * 28 / * 28
18. 18. Additional exclusion criteria only applicable for mFOLFIRINOX treatment: Has known fructose intolerance (malabsorption)
19. 19. Additional exclusion criteria only applicable for mFOLFIRINOX treatment: Has complete dihydropyrimidine dehydrogenase (DPD) deficiency
20. 20. Additional exclusion criteria only applicable for gemcitabine plus nab-paclitaxel treatment: Has a history of slowly progressive dyspnea and unproductive cough, or of conditions such as sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity, pneumonitis or multiple allergies
21. 21. Additional exclusion criteria only applicable for gemcitabine plus nab-paclitaxel treatment: Has a history of Peripheral Artery Disease (eg, claudication, Leo Buerger's disease)
22. 22. Additional exclusion criteria only applicable for gemcitabine plus nab-paclitaxel treatment: Has a history of connective tissue disorders (eg, lupus, scleroderma, arteritis nodosa)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part 1: Incidence of DLTs
2. Part 2 and Part 3: Objective response rate (ORR).

Secondary endpoints 11

1. Best Overall Response (BOR), with response categories CR, PR, SD, and PD
2. Duration of response (DoR)
3. Duration of SD
4. Disease control rate
5. Time to next anti-cancer therapy
6. Progression-free survival (PFS)
7. Overall survival (OS)
8. Type, frequency and severity of AEs
9. Detection and characterization of anti-drug antibody (ADA) titers in serum
10. PK parameters will include Cmax, Tmax, and AUC(0-T). Additional parameters may be calculated depending on data obtained
11. Part 1: Objective response rate (ORR)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 11

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Alligator Bioscience AB

Sponsor organisation

Alligator Bioscience AB

Address

Medicon Village

City

Lund

Postcode

223 81

Country

Sweden

Scientific contact point

Organisation

Alligator Bioscience AB

Contact name

Sumeet Ambarkhane

Public contact point

Organisation

Alligator Bioscience AB

Contact name

Karin Nordbladh

Third parties 6

Locations

3 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 45 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications