An Open-Label Multicenter 3-Arm Randomized Phase 2 Study to Assess the Efficacy and Safety of TTX-030 and Chemotherapy With or Without Budigalimab, Compared to Chemotherapy Alone, for the Treatment of Patients not Previously Treated for Metastatic Pancreatic Adenocarcinoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Trishula Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Digestive System Diseases [C06]

Trial duration

25 Jun 2024 → 4 Mar 2026

Decision date (initial)

2024-05-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AbbVie Inc. · Trishula Therapeutics, Inc.

External identifiers

EU CT number

2023-508356-19-00

ClinicalTrials.gov

NCT06119217

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To evaluate the benefit of the addition of TTX-030 with or without budigalimab to nab-paclitaxel + gemcitabine in the target population

Secondary objectives 2

1. 'To evaluate the benefit of the addition of TTX-030 with or without budigalimab to nab-paclitaxel + gemcitabine in the overall population and in the target population
2. 'To evaluate the safety profile observed with the addition of TTX-030 with or without budigalimab in combination with nab-paclitaxel + gemcitabine

Conditions and MedDRA coding

Pancreatic adenocarcinoma metastatic

Study design 2 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. Male or female subjects ≥18 years of age at the time of screening.
3. Histologically or cytologically confirmed diagnosis of metastatic PDAC.
4. No prior systemic treatment for metastatic disease. Prior neoadjuvant or adjuvant systemic chemotherapy is permitted in the absence of disease progression within 6 months following last dose of chemotherapy.
5. No prior treatment with therapeutics specifically targeted to enhancing or de-repressing anti-tumor immunity including but not limited to checkpoint inhibitors or agents targeting the adenosine pathway (CD39, CD73 or adenosine receptor inhibitors).
6. Evidence of measurable disease as assessed by the investigator per RECIST 1.1.
7. Appropriate for treatment with nab-paclitaxel and gemcitabine chemotherapy.
8. Availability of tumor tissue (obtained by biopsy during screening, or archival if collected within 90 days prior to the first dose of study drug and in the absence of intervening therapy). Subjects with contraindications for a biopsy procedure and without acceptable archival tissue samples are not eligible.
9. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
10. Subject must weigh ≥35 kg.
11. Resolution of adverse events from any prior chemotherapy, immunotherapy, or prior systemic anticancer therapy, radiotherapy, or surgery to Grade 1 or baseline (except Grade 2 alopecia and Grade 2 sensory neuropathy).
12. Women of childbearing potential and all men must agree to use 2 highly effective methods of contraception through 6 months (180 days) after the last administration of any study treatment. Note: Highly effective contraception methods include total abstinence; female sterilization (tubal ligation, bilateral oophorectomy, and/or hysterectomy); male sterilization (at least 6 months prior to Screening); intrauterine device or intrauterine hormone-releasing system; oral, injected, or implanted hormonal contraception with only progestogen at least 30 days before first dose; AND barrier methods of contraception; oral, injectable, transdermal, or intravaginal combined hormonal contraception with estrogen and progestogen at least 30 days before first dose (Prescribing information should be followed if different from the above).
13. Subjects with history of congestive heart failure must have cardiac echocardiogram (ECHO) or multigated acquisition (MUGA) scan indicating left ventricular ejection fraction ≥45% within 28 days prior to the first dose of study treatment.
14. Required baseline laboratory tests: a. Hematology: absolute neutrophil count (ANC) ≥1.2 k/μL, platelets ≥100 k/μL, hemoglobin (Hgb) ≥9 g/dL b. Coagulation: prothrombin time (PT) and International Normalized Ratio (INR) ≤1.2 x upper limit of normal (ULN), except for subjects receiving anticoagulation; subjects must be on a stable dose of warfarin for 6 weeks prior to enrollment. c. Kidney: Creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR) ≥40 mL/min calculated by Cockcroft-Gault or CKD-EPI (Appendix 6) d. Liver: AST and ALT ≤2.5 x ULN (or ≤5 x ULN with hepatic metastases); total bilirubin ≤2 x ULN (or ≤3 x ULN with Gilbert’s syndrome); serum albumin ≥3.0 g/dL

Exclusion criteria 12

1. History of clinically significant allergy or hypersensitivity to planned study treatment components or to any monoclonal antibody (defined as any Grade 3 reaction lasting ≥48 hours despite optimal therapy)
2. History of SJS, Toxic epidermal necrolysis (TEN), or drug reaction with eosinophilia and systemic symptoms (DRESS)
3. History of autoimmune disease including but not limited to rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, non-infectious pneumonitis, interstitial lung disease (ILD), requiring systemic treatment that required systemic steroids or immunosuppressive agents within the last 2 years. Subjects with findings consistent with active autoimmune disease on screening evaluation (computed tomography [CT] showing pneumonitis or ILD, physical examination findings) are not eligible. NOTE: History of vitiligo, autoimmune thyroiditis, or mild psoriasis are allowed.
4. Any active disease requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days prior to Day 1 of treatment. (NOTE: Inhaled, intranasal, intra-articular and topical [including ocular] steroids are allowed. Adrenal replacement [i.e., physiologic replacement] doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease).
5. History of primary immunodeficiency, bone marrow transplantation, chronic lymphocytic leukemia, solid organ transplantation, or previous clinical diagnosis of tuberculosis
6. Use of investigational agent within 14 days prior to the first dose of study drug
7. Evidence of active central nervous system (CNS) metastatic disease or carcinomatous meningitis
8. Known history of human immunodeficiency virus (HIV) or other chronic immunodeficiency
9. Women who are pregnant or breastfeeding
10. Subject has received live vaccine within 28 days prior to the first dose of study drug
11. The subject has had major surgery per the Investigator within 28 days prior to the first dose of study drug, and the surgical wound is not adequately healed. A diagnostic or research biopsy does not exclude subjects from enrollment. Placement of a vascular access device such as a Port-A-Cath is not considered major surgery.
12. Has uncontrolled intercurrent illness including, but not limited to: a. Uncontrolled diabetes b. New York Heart Association (NYHA) Class 3 or 4 congestive heart failure c. Unstable angina, arrhythmia, or myocardial infarction within 6 months prior to screening d. Poorly controlled hypertension, defined as a blood pressure consistently above 160/90 mmHg despite optimal medical management e. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters (e.g., PleurX®) are allowed f. Active or chronic viral hepatitis B or C infection g. Uncontrolled thyroid disease h. Active infection requiring systemic therapy; subjects receiving ongoing systemic antibiotic, antiviral or antifungal therapy for maintenance should be discussed with the medical monitor prior to screening and enrollment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression-free survival (PFS)

Secondary endpoints 2

1. Progression-free survival, Objective response rate, Duration of response, Overall survival (PFS, ORR, DoR, OS)
2. Type, severity, and frequency of treatment-emergent AEs

Investigational products

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

Test 2

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Trishula Therapeutics Inc.

Sponsor organisation

Trishula Therapeutics Inc.

Address

2268 Westborough Boulevard Suite 302-263

City

South San Francisco

Postcode

94080-5439

Country

United States

Scientific contact point

Organisation

Trishula Therapeutics Inc.

Contact name

Siddhartha Mitra, MD PHD, Chief Medical Officer

Public contact point

Organisation

Trishula Therapeutics Inc.

Contact name

Anh Tran, Exec. Director, Clinical Operations

Third parties 10

Locations

4 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Unexpected events 1 · Art. 53 CTR

Note: SUSARs are reported via EudraVigilance, not CTIS — events shown here are CTIS-public notifications only.

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 21 files

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

Application history

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