Safety and Preliminary Efficacy Assessment of AZD7789 in Patients With Relapsed or Refractory Classical Hodgkin Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

16 Jun 2022 → 5 Sep 2025

Decision date (initial)

2024-02-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2022-502773-41-00

EudraCT number

2021-003569-36

ClinicalTrials.gov

NCT05216835

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

Part A Dose Escalation: To assess the safety and tolerability of sabestomig in participants with r/r cHL. To establish the maximum tolerated dose, or optimal biological dose, and recommended Phase 2 dose.

Part B Dose Expansion (all): To assess the safety and tolerability of sabestomig in participants with r/r cHL.

Part B Dose Expansion (B1): To assess the preliminary antitumor activity of sabestomig in participants with r/r cHL (anti-PD-1/PD-L1 exposed).

Part B Dose Expansion (B2): To assess the preliminary antitumor activity of sabestomig in patients with r/r cHL (anti PD-1/PD-L1 naïve).

Secondary objectives 3

1. Part A Dose Escalation: To assess the preliminary antitumor activity of sabestomig in participants with r/r cHL
2. Part B Dose Expansion: To further assess the preliminary antitumor activity of sabestomig in participants with r/r cHL To evaluate Patient Reported treatment-related symptoms, overall side-effect impact and overall global health status while on sabestomig.
3. Part A Dose Escalation and Part B Dose Expansion: To assess the PK of sabestomig in participants with r/r cHL To assess the immunogenicity of sabestomig in participants with r/r cHL

Conditions and MedDRA coding

Relapsed/Refractory Classical Hodgkin Lymphoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Must be ≥ 16 years of age at the time of obtaining informed consent
2. 2. Eastern Cooperative Oncology Group performance status of 0 or 1 at screening
3. 3. Must have at least one PET-avid measurable lesion according to Modified Lugano Criteria after the last line of therapy.
4. 4. Confirmed histological diagnosis of active relapse/refractory cHL
5. 5. Must have failed at least 2 prior lines of systemic therapy. In part A dose escalation the prior lines of therapy must include at least 3 cycles of anti-PD- 1/PD-L1 and in part B dose expansion at least 2 cycles of an anti-PD-1/PD-L1. In part B dose expansion cohort B2, prior antiPD-1/PD-L1 therapy is excluded. For all participants, no previous treatment with anti- TIM-3 is allowed. Previous anti-CTLA-4 treatment is acceptable with at least 2 months washout period prior to study entry.
6. 6. Adequate organ and bone marrow function
7. 7. Non-pregnant women and willingness of female participants to avoid pregnancy or male participants willing to avoid fathering children through highly effective methods of contraception
8. 8. Minimum body weight ≥ 40 kg for all participants.

Exclusion criteria 14

1. 1. Unresolved toxicities of ≥ Grade 2 from prior therapy, unless immune-mediated.
2. 2. Any prior ≥ Grade 3 imAE while receiving prior checkpoint inhibitor immunotherapy or any unresolved imAE ≥ Grade 2
3. 3. Participants with CNS involvement or leptomeningeal disease.
4. 4. History of organ transplant or allogeneic stem cell transplant; autologous stem cell transplant and CAR-T based therapies are permitted if completed >3 months prior to study entry
5. 5. Any venous or arterial thromboembolic event within ≤ 6 months prior to the first dose of study intervention.
6. 6. Infectious disease exclusions: Active infection including TB, HIV, active hepatitis A, chronic or active hepatitis B, chronic or active hepatitis C, active COVID-19 infection
7. 7. History of arrhythmia which is requires treatment; symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia
8. 8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics, cardiomyopathy of any etiology, symptomatic congestive heart failure, uncontrolled hypertension, uncontrolled diabetes mellitus, unstable angina pectoris, history of myocardial infarction within the past 6 months, history of myocarditis, serious chronic gastrointestinal conditions associated with diarrhea, active noninfectious skin disease.
9. 9. Active or prior documented pathologically confirmed autoimmune or inflammatory disorders, including inflammatory bowel disease (e.g, colitis or Crohn's disease), diverticulitis, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc. some exceptions have been specified in the protocol
10. 10. Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD or active pneumonitis.
11. 11. Other invasive malignancy within 2 years prior to screening
12. 12. Congenital long QT syndrome or history of QT prolongation associated with other medications that cannot be changed or discontinued based on a cardiologist assessment
13. 13. Current or prior use of immunosuppressive medication within 14 days prior to the first dose of study intervention
14. 14. Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for noncancer-related conditions is acceptable

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part A Dose Escalation: Incidence of AEs, imAEs, and SAEs Incidence of AEs leading to discontinuation of sabestomig Changes from baseline and clinically significant alterations in vital signs, laboratory parameters, and ECG results Incidence of dose-limiting toxicities
2. Part B Dose Expansion (all): Incidence of AEs, imAEs, and SAEs Incidence of AEs leading to discontinuation of sabestomig Changes from baseline and clinically significant alterations in vital signs, laboratory parameters, and ECG results
3. Part B Dose Expansion (B1): Objective Response Rate (defined as the proportion of patients with complete remission or partial remission)
4. Part B Dose Expansion (B2): Complete Response Rate (defined as the proportion of patients with complete remission)

Secondary endpoints 3

1. Part A Dose Escalation: Complete Response Rate, Objective Response Rate, DoR, and DoCR and PFS including landmarks at 12 and 24 months OS including landmarks at 12 and 24 months
2. Part B Dose Expansion: DoR, DoCR and PFS including landmarks at 12 and 24 months OS including landmarks at 12 and 24 months Proportion of dosed subjects over time with: diarrhea, rash, and fatigue (PRO-CTCAE or Peds-PROCTCAE) overall side-effect bother (PGI-TT) quality of life/health (EORTC ILXX QL2)
3. Part A Dose Escalation and Part B Dose Expansion: PK parameters including the maximum observed concentration, area under the concentration-time curve, clearance and terminal elimination half life • Incidence of anti-drug antibodies against sabestomig in serum

Investigational products

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

Test 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Third parties 1

Locations

4 EU/EEA countries · 8 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 14 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