Clinical Trial of SOT102 Antibody Drug Conjugate in Patients With Advanced Gastric and Pancreatic Adenocarcinoma (CLAUDIO-01)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

SOTIO Biotech a.s.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

29 Jun 2022 → 13 Dec 2024

Decision date (initial)

2023-09-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

SOTIO Biotech a.s.

External identifiers

EU CT number

2023-504441-31-00

EudraCT number

2021-005873-25

ClinicalTrials.gov

NCT05525286

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Efficacy, Dose response, Safety

Part A and Part B
To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of SOT102 given as monotherapy and in combination with first-line SoC treatment. MTD is defined as the highest dose level tested below the dose level associated with ≥33% of dose-limiting toxicity (DLT)-evaluable patients experiencing a DLT. The RP2D will be selected based on integrated evaluation of the totality of clinical and preclinical data, for all dose levels tested.
Part C and Part D
To assess the efficacy of SOT102 in monotherapy and in combination with first-line SoC treatment by objective response rate

Secondary objectives 9

1. To assess the safety and tolerability of SOT102 in monotherapy and in combination with first-line SoC treatment by the occurrence of DLTs, occurrence of treatment-emergent AEs (TEAEs), SOT102-related AEs, serious AEs (SAEs), AEs leading to premature discontinuation of SOT102, deaths, or clinical laboratory test abnormalities
2. To characterize the pharmacokinetics (PK) of total SOT102, conjugated SOT102, PNU159682, PNU-ethylene diamine (EDA), PNU-EDA-GGT (M4), PNU-EDA-GG (M5), and PNU-EDA-G (M6)
3. To explore evidence of SOT102 activity in monotherapy and in combination with first-line SoC treatment in individual patients by anecdotal tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by type and CLDN18.2 expression
4. To explore whether patients develop any antibodies against SOT102 by the number of patients with detected antibodies against any part of SOT102 Part C and Part D
5. To evaluate additional measures of efficacy of SOT102 in monotherapy and in combination with first-line SoC treatment by duration of response, progression-free survival per RECIST 1.1, clinical benefit rate per RECIST 1.1 (Part C only), overall survival
6. To assess the safety and tolerability of SOT102 in monotherapy and in combination with first-line SoC treatment by the occurrence of TEAEs, SOT102-related AEs, SAEs, AEs leading to premature discontinuation of SOT102, deaths, or clinical laboratory test abnormalities
7. To assess quality of life (QoL) after treatment with SOT102 in monotherapy and in combination with first-line SoC treatment by assessment of global and disease-specific QoL by patient-reported questionnaires EORTC QLQ-C30 and EORTC QLQ-PAN26 for patients with pancreatic cancer
8. To characterize the PK of total SOT102, conjugated SOT102, PNU159682, PNU-EDA, PNU-EDA-GGT (M4), PNU-EDA-GG (M5), and PNU-EDA-G (M6)
9. To explore whether patients develop any antibodies against SOT102 by the number of patients with detected antibodies against any part of SOT102

Conditions and MedDRA coding

gastric adenocarcinoma or adenocarcinoma of the gastroesophageal junction (GEJ) and pancreatic adenocarcinoma

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Medicines And Healthcare Products Regulatory Agency, Food And Drug Administration, Medicines Evaluation Board

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 34

1. Age ≥18 years
2. Patient is, in the judgement of the investigator, an appropriate candidate for experimental therapy
3. Patient agrees not to participate in other interventional clinical trials while enrolled in the present trial (with the exception of survival follow-up period)
4. All previous cancer therapies for locally advanced gastric/pancreatic cancer and any agents that have not received regulatory approval for any indication must have been discontinued prior to day 1 of cycle 1 (Note: not applicable in France).
5. Adequate tumor tissue from biopsy or fine needle aspiration (FNA) (formalin-fixed paraffin-embedded [FFPE] blocks), or unstained slides from archival biopsy available or willingness to undergo a fresh tumor biopsy.
6. Part A- Patient has advanced inoperable or metastatic disease
7. Part A- Patient has received and/or has been determined to be intolerant of all SoC therapy known to confer clinical benefit
8. Part A- Measurable or non-measurable disease according to RECIST 1.1
9. Part A- Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced or metastatic
10. Part B- Adequate tumor tissue or cytology sample (FFPE blocks) or unstained slides from archival biopsy available or willingness to undergo a fresh tumor biopsy
11. Part B- Patient has advanced inoperable or metastatic disease
12. Written informed consent given prior to any trial-specific procedures
13. Part B- Patient must have at least one measurable lesion according to RECIST 1.1
14. Part B - Patients with gastric/GEJ adenocarcinoma (gastric B) - Histological or cytological evidence of adenocarcinoma of the stomach or GEJ that is advanced or metastatic
15. Part B- Patients with gastric/GEJ adenocarcinoma (gastric B) - Must have HER2-negative tumors
16. Part B- Patients with pancreatic adenocarcinoma (pancreatic B) Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced or metastatic
17. Part C- Adequate tumor tissue or cytology sample (FFPE blocks) or unstained slides from archival biopsy available or willingness to undergo a fresh tumor biopsy. Tumor sample must have CLDN18.2 expression using a central immunohistochemistry method.
18. Part C- Patient has advanced inoperable or metastatic disease
19. Part C- Measurable disease according to RECIST 1.1.
20. Part C- Patients with gastric/GEJ adenocarcinoma (gastric C) - Must have received at least two prior systemic therapies for advanced or metastatic disease. If HER2 overexpression: must have received anti-HER2 therapy.
21. Part C- Patients with pancreatic adenocarcinoma (pancreatic C) - Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced or metastatic
22. Adequate organ function as assessed by the following parameters: hematologic; hepatic; renal; prothrombin time/international normalized ratio (INR); albumin; proteinuria; Serum concentrations of potassium, magnesium, and calcium within normal range
23. Part C- Patients with pancreatic adenocarcinoma (pancreatic C) - Must have received at least one prior systemic therapy for advanced or metastatic disease If HER2 overexpression: must have received anti-HER2 therapy.
24. Part D- Adequate tumor tissue or cytology sample (FFPE blocks) or unstained slides from archival biopsy available or willingness to undergo a fresh tumor biopsy. Tumor sample must have CLDN18.2 expression using a central immunohistochemistry method.
25. Part D- Patient must have at least one measurable lesion according to RECIST 1.1. At least one measurable lesion must be outside of an earlier radiation field or must have progressed after radiation therapy
26. Part D- Patients with gastric/GEJ adenocarcinoma (gastric D) - Histological or cytological evidence of adenocarcinoma of the stomach or GEJ that is advanced inoperable or metastatic
27. Part D- Patients with gastric/GEJ adenocarcinoma (gastric D) - Must have HER2-negative tumors
28. Part D- Patients with pancreatic adenocarcinoma (pancreatic D) - Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced inoperable or metastatic
29. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
30. Estimated life expectancy ≥3 months as per investigator’s assessment
31. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and one of the following conditions applies: Not a woman of childbearing potential (WOCBP). A WOCBP is defined as fertile, following menarche and until becoming postmenopausal unless permanently sterile. A WOCBP who agrees to use a highly effective contraceptive method during the treatment period and for at least 9 months after the last dose of SOT-102 or first-line SoC treatment (whichever occurs later)
32. Male patients must agree to use a condom during treatment and for 9 months after SOT102 or first-line SoC treatment discontinuation. Male pat wishing to become a father during or after the trial should consider sperm preservation. WOCBP partner of male part should use highly effective contraception methods for 9 months after SOT102 or first-line SoC treat discontinuation.
33. Left ventricular ejection fraction (LVEF) ≥50% as determined by echocardiography or nuclear medicine methodology (multiple gated acquisition scanning [MUGA])
34. QTcF interval <450 msec on screening electrocardiogram (ECG)

Exclusion criteria 25

1. Patients with hepatitis B will be eligible if: •there is serologic evidence of a resolved prior HBV infection (HBsAg-negative and anti-HBc–positive
2. Patients with hepatitis C will be eligible if: •they have completed curative antiviral treatment and have HCV viral load below the limit of quantification
3. Alcohol or drug abuse as determined by the investigator
4. Psychiatric condition or social situation that, in the opinion of the investigator, preclude that the patient is able to comply with trial requirements
5. New York Heart Association class ≥2 heart failure, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, myocardial infarction, cerebrovascular accident or hypertensive crisis within 6 months prior to day 1 of cycle 1
6. History of major ventricular arrhythmias
7. History or family history of congenital long QT syndrome
8. Bradycardia (<50 beats per minute)
9. Family history of sudden cardiac death before age 50
10. Major surgical intervention ≤28 days prior to ICF signature or incomplete wound healing after surgical intervention
11. Patient has received radiation therapy ≤14 days before day 1 of cycle 1 or has not recovered to grade ≤1 from treatment-related side effects
12. Hypersensitivity or intolerance to any component of trial intervention
13. Time since last transfusion of RBCs ≤14 days before cycle 1 day 1
14. Exclusion criteria specific to Part A Part C - Any prior systemic therapy for metastatic cancer other than gastric or pancreatic cancer.
15. Exclusion criteria specific to Part B -General -Patients must not have received any systemic therapy for metastatic disease. Patients must not have received any prior systemic therapy for metastatic cancer other than gastric or pancreatic cancer. Patients with contraindications to any component of the first-line SoC treatment Patients with clinically active inflammatory bowel disease
16. Exclusion criteria specific to Part B - Patients with pancreatic adenocarcinoma (pancreatic B) Patients more clinically suitable (e.g., with BRCA1/2 mutation) to receive treatment with leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin (FOLFIRINOX) as compared to nab-paclitaxel and gemcitabine according to the investigator’s opinion
17. Exclusion criteria specific to Part D- General - Patients must not have received any systemic therapy for metastatic disease. Patients must not have received any prior systemic therapy for metastatic cancer other than gastric or pancreatic cancer. Patients with contraindications to any component of the first-line SoC treatment Patients with clinically active inflammatory bowel disease
18. Exclusion criteria specific to Part D- Patients with pancreatic adenocarcinoma (pancreatic D) Patients more clinically suitable (e.g., with BRCA1/2 mutation) to receive treatment with FOLFIRINOX as compared to nab-paclitaxel and gemcitabine according to the investigator’s opinion
19. Patient has been previously treated with the maximum cumulative dose of anthracyclines
20. Severe preexisting medical conditions as per judgement of the investigator
21. History of interstitial pneumonitis or pulmonary fibrosis
22. Symptomatic central nervous system malignancy. Patients with asymptomatic or treated central nervous system metastases may be eligible if they are not treated with corticosteroids or anticonvulsants and the disease is stable for at least 60 days.
23. Patient has peripheral sensory neuropathy grade ≥2
24. Active infection requiring systemic therapy that is not clinically controlled before the signature of the ICF
25. Patients with HIV will be eligible if •CD4+ T-cell (CD4+) counts ≥350 cells/uL •they have no history of AIDS-defining opportunistic infections •they are not currently on HIV therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part A and B •To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of SOT102 given as monotherapy and in combination with first-line standard of care (SoC) treatment. MTD is defined as the highest dose level tested below the dose level associated with ≥33% of dose-limiting toxicity (DLT)-evaluable patients experiencing DLT. The RP2D will be selected based on integrated evaluation of the totality of clinical and preclinical data, for all dose levels tested.
2. Part C and D •To assess the efficacy of SOT102 in monotherapy and in combination with first-line SoC treatment by objective response rate

Secondary endpoints 4

1. The occurrence of DLTs, occurrence of treatment-emergent AEs (TEAEs), SOT102- related AEs, serious AEs (SAEs), AEs leading to premature discontinuation of SOT102, deaths, or clinical laboratory test abnormalities
2. PK of total SOT102, conjugated SOT102, PNU159682, PNU-EDA, -EDA-GGT (M4), PNU-EDA-GG (M5), and PNU-EDA-G (M6)
3. Anecdotal tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by type and CLDN18.2 expression. The number of patients with detected antibodies against any part of SOT102
4. Additionally for Part C & Part D DoR, PFS and clinical benefit rate per RECIST 1.1, OS Assessment of global and disease-specific QoL by patient-reported questionnaires EORTC QLQ-C30 and EORTC QLQ-STO22 for patients with gastric cancer, and EORTC QLQC30 and EORTC QLQ-PAN26 for patients with pancreatic cancer

Investigational products

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

Test 1

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

SOTIO Biotech a.s.

Sponsor organisation

SOTIO Biotech a.s.

Address

Jankovcova 1518/2, Holesovice Holesovice

City

Prague 7

Postcode

170 00

Country

Czechia

Scientific contact point

Organisation

SOTIO Biotech a.s.

Contact name

Richard Kapsa

Public contact point

Organisation

SOTIO Biotech a.s.

Contact name

Richard Kapsa

Third parties 4

Locations

4 EU/EEA countries · 6 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

Temporary halts 4 · Art. 38 CTR

Urgent safety measures 1 · Art. 54 CTR

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 2 files

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

Application history

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