A Study of Two Dose Levels of Vobramitamab Duocarmazine in Participants with Metastatic Castration-resistant Prostate Cancer (TAMARACK)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Macrogenics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

15 May 2023 → 24 Jan 2025

Decision date (initial)

2023-02-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

MacroGenics, Inc.

External identifiers

EU CT number

2022-501078-20-00

ClinicalTrials.gov

NCT05551117

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

To evaluate the efficacy of vobramitamab duocarmazine at two dose levels as measured by Radiographic Progression Free Survival (rPFS) by investigator assessment using Prostate Cancer Working Group 3 (PCWG3) criteria.

Secondary objectives 6

1. 1. To characterize the frequency and severy of AEs and overall tolerability observed with vobramitamab duocarmazine when administered at 2.0 mg/kg and 2.7 mg/kg IV Q4W.
2. 2. To evaluate the efficacy of vobramitamab duocarmazine as measured by prostate-specific antigen (PSA).
3. 3. To evaluate the efficacy of vobramitamab duocarmzaine in participants with RECIST-evaluable disease as measured by objective response rate (ORR) and Duration of Response (DoR) by investigator assessment.
4. 4. To evaluate the effect of vobramitamab duocarmazine on SSEs.
5. 5. To characterize the PK of vobramitamab duocarmazine.
6. 6. To characterize immunogenicity of vobramitamab duocarmazine.

Conditions and MedDRA coding

Metastatic Castration-resistant Prostate Cancer

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Histologically confirmed adenocarcinoma of the prostate without evidence of neuroendocrine differentiation, signet cell, or small cell features
2. 2. Participants must have ≥ 1 metastatic lesion that is present on magnetic resonance imaging (MRI), computed tomography (CT), or bone scan obtained ≤ 28 days prior to initiation of study treatment
3. 3. Tumor progression at study entry documented by PSA or imaging per PCWG3 criteria
4. 4. Received 1 prior ARAT for metastatic or non-metastatic, castrationsensitive or castration-resistant prostate cancer. A second ARAT regimen of < 60 days used as bridging to lutetium-177 is permitted.
5. 5. Availability of archival or formalin-fixed paraffin-embedded (FFPE) tumor tissue sample for participants with metastasis to internal organs
6. 6. Acceptable physical condition and laboratory value

Exclusion criteria 10

1. 2. Any underlying medical or psychiatric condition impairing participant's ability to receive, tolerate, or comply with the planned treatment or study procedures
2. 3. Received >1 prior taxane-containing regimen for prostate cancer. A second taxane regimen of < 60 days used as bridging for lutetium-177 is permitted.
3. 5. Another hematologic or solid tumor ≥ stage 1 malignancy that completed surgery, last dose of radiotherapy, or last dose of systemic anti-cancer therapy ≤ 2 years from first dose of study treatment. Participants who had curative therapy for localized malignancy are eligible
4. 6. Untreated, symptomatic central nervous system (CNS) metastasis
5. 7. Prior treatment with any B7-H3 targeted agent for cancer
6. 8. Contraindications to the use of corticosteroid treatment
7. 9. Prior stem cell, tissue, or solid organ transplant
8. 1. Use of products that have published anti-prostate cancer activity or are known to decrease PSA.
9. 4. Participants with a known history of BRCA mutation (germline or somatic) are not eligible unless they received prior treatment with a PARP inhibitor where available, indicated and tolerated.
10. 10. Received > 3 total prior therapies for mCRPC.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. rPFS per PCWG3 criteria

Secondary endpoints 11

1. PSA response rate per PCWG3 criteria
2. Time to PSA progression per PCWG3 criteria
3. Duration of PSA response per PCWG3 criteria
4. PSA percent change over time
5. Best PSA percent change
6. ORR by investigator assessment per PCWG3 criteria
7. DoR by investigator assessment per PCWG3 criteria
8. Time to first symptomatic skeletal event (SSE)
9. Number of participants with adverse event (AEs), serious AEs (SAEs), and AEs leading to study treatment discontinuation.
10. Concentrations and PK parameters for vobramitamab duocarmazine (and metabolites as appropriate)
11. Incidence of anti-drug antibodies (ADA) formation against vobramitamab duocarmazine

Investigational products

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

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Macrogenics Inc.

Sponsor organisation

Macrogenics Inc.

Address

9704 Medical Center Drive

City

Rockville

Postcode

20850-3343

Country

United States

Scientific contact point

Organisation

Macrogenics Inc.

Contact name

Global Trial Manager

Public contact point

Organisation

Macrogenics Inc.

Contact name

Global Trial Manager

Third parties 10

Sponsor responsibilities

Article 77 implementation

Macrogenics Inc.

Locations

7 EU/EEA countries · 50 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 53 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