A Phase 2 Study of Elranatamab (PF-06863135) Monotherapy in Participants With MM Who Are Refractory to at Least One PI, One IMiD and One Anti-CD38 mAb

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Aug 2021 → ongoing

Decision date (initial)

2024-09-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2023-504479-25-00

EudraCT number

2020-004533-21

ClinicalTrials.gov

NCT04649359

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Pharmacogenomic, Efficacy, Safety, Therapy

To determine the efficacy of elranatamab in Cohort A and Cohort B.

Secondary objectives 5

1. To determine additional efficacy of elranatamab in Cohort A.
2. To determine additional efficacy of elranatamab in Cohort A and Cohort B.
3. To determine the safety and tolerability of elranatamab.
4. To evaluate the PK of elranatamab.
5. To evaluate the immunogenicity of elranatamab.

Conditions and MedDRA coding

Multiple myeloma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 1. Male or female participants age ≥18 years. • A female participant is eligible to participate if she is not pregnant or breastfeeding.
2. 2. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
3. 3. Prior diagnosis of MM as defined according to IMWG criteria.
4. 4. Measurable disease based on IMWG criteria as defined by at least 1 of the following: a. Serum M-protein >0.5 g/dL by SPEP b. Urinary M-protein excretion >200 mg/24 hours by UPEP c. Serum immunoglobulin FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FLC ratio (<0.26 or >1.65).
5. 5. Refractory to at least one IMiD.
6. 6. Refractory to at least one PI.
7. 7. Refractory to at least one anti-CD38 antibody.
8. 8. Relapsed or refractory to last anti-MM regimen. Note: Refractory is defined as having disease progression while on therapy or within 60 days of last dose in any line, regardless of response.
9. 9. Cohort A: Has not received prior BCMA-directed therapy. Cohort B: Has received prior BCMA-directed ADC or BCMA-directed CAR T-cell therapy, either approved or investigational.
10. 10. ECOG performance status ≤2.
11. 11. LVEF ≥40% as determined by a MUGA scan or ECHO.
12. 12. Adequate hepatic function characterized by the following: a. Total bilirubin ≤2 x ULN (≤3 x ULN if documented Gilbert’s syndrome); b. AST ≤2.5 x ULN; and c. ALT ≤2.5 x ULN.
13. 13. Adequate renal function defined by an estimated creatinine clearance ≥30 mL/min (according to the Cockcroft Gault formula, by 24-hour urine collection for creatinine clearance, or according to local institutional standard method).
14. 14. Adequate BM function characterized by the following: a. ANC ≥1.0 × 109/L (use of granulocyte-colony stimulating factors is permitted if completed at least 7 days prior to planned start of dosing); b. Platelets ≥25 × 109/L (transfusion support is permitted if completed at least 7 days prior to planned start of dosing); and c. Hemoglobin ≥8 g/dL (transfusion support is permitted if completed at least 7 days prior to planned start of dosing).
15. 15. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1.
16. 16. Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion criteria 17

1. 1. Smoldering MM.
2. 10. Active HBV, HCV, SARS-CoV2, HIV, or any active, uncontrolled bacterial, fungal, or viral infection. Active infections must be resolved at least 14 days prior to enrollment.
3. 11. Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.
4. 12. Other surgical (including major surgery within 14 days prior to enrollment), medical or psychiatric conditions including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
5. 2. Active plasma cell leukemia.
6. 3. Amyloidosis.
7. 4. POEMS syndrome.
8. 5. Stem cell transplant within 12 weeks prior to enrollment or active GVHD.
9. 6. Impaired cardiovascular function or clinically significant cardiovascular diseases, defined as any of the following within 6 months prior to enrollment: a. Acute myocardial infarction or acute coronary syndromes (eg, unstable angina, coronary artery bypass graft, coronary angioplasty or stenting, symptomatic pericardial effusion); b. Clinically significant cardiac arrhythmias (eg, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia); c. Thromboembolic or cerebrovascular events (eg, transient ischemic attack, cerebrovascular accident, deep vein thrombosis [unless associated with a central venous access complication] or pulmonary embolism); d. Prolonged QT syndrome (or triplicate average QTcF >470 msec at screening).
10. 7. Ongoing Grade ≥2 peripheral sensory or motor neuropathy.
11. 8. History of any grade peripheral sensory or motor neuropathy with prior BCMA-directed therapy (Cohort B).
12. 9. History of GBS or GBS variants, or history of any Grade ≥3 peripheral motor polyneuropathy.
13. Prior/Concomitant Therapy: 13. Previous treatment with an anti-BCMA bispecific antibody.
14. Prior/Concurrent Clinical Study Experience: 14. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).
15. Other Exclusions: 15. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
16. 16. Known or suspected hypersensitivity to the study intervention or any of its excipients.
17. 17. Live attenuated vaccine must not be administered within 4 weeks of the first dose of study intervention.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. • ORR by BICR per IMWG.

Secondary endpoints 13

1. • ORR by BICR baseline EMD status per IMWG.
2. • DOR by BICR and investigator per IMWG.
3. • CRR by BICR and investigator per IMWG.
4. • ORR by investigator per IMWG.
5. • DOCR by BICR and investigator per IMWG.
6. • PFS by BICR and investigator per IMWG.
7. • TTR by BICR and investigator per IMWG.
8. • MRD negativity rate (central lab) per IMWG.
9. • AEs and laboratory abnormalities as graded by NCI CTCAE v5.0.
10. • Severity of CRS and ICANS assessed according to ASTCT criteria.
11. • Pre- and postdose concentrations of elranatamab.
12. • ADAs and NAbs against elranatamab.
13. • OS.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 3

Locations

5 EU/EEA countries · 13 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 44 files

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

Application history

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