A Study to Evaluate the Safety,Tolerability, Pharmacokinetics and Clinical Activity of Mocertatug Rezetecan for Injection in Participants With Advanced Solid Tumors (BEHOLD-1)

GlaxoSmithKline (GSK)

Status and phase: Enrolling; Phase 1

Conditions: Neoplasms; Solid Tumors

Treatments: Drug: Mocertatug rezetecan

Study type: Interventional

Funder types: Industry

Identifiers

NCT06431594

2024-513860-25 (Other Identifier)

222730

Details and patient eligibility

About

The goal of this study is to assess the safety and tolerability of Mocertatug Rezetecan . The study will also see how the levels of Mo-Rez change over time at different dose amount

Enrollment: 675 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Males or females aged 18 years or older (≥18 years).

• Participants with pathologically confirmed advanced solid tumor (who have failed or are intolerant to standard of care.

• PROC cohort

  1. Histologically documented, advanced (metastatic and/or unresectable) high-grade serous/endometrioid ovarian, primary peritoneal, or fallopian tube cancer.
  2. Must have received or are intolerant to 1 but no more than 4 lines of prior systemic therapy.
  3. Platinum-resistant disease, defined as progression or relapse within 6 months after the completion of platinum-based therapy.
  4. Must have had prior bevacizumab , unless there is a documented contraindication or intolerance.
  5. Participants with known Folate receptor-α (FR-α) expressing tumors must have received mirvetuximab soravtansine if the regimen is locally available, unless there is a documented contraindication or intolerance.

Participants with known Breast cancer susceptibility gene (BRCA) mutated tumors should have received a Poly adenosine diphosphate-ribose polymerase (PARP) inhibitor if the regimen is locally available, unless there is a documented contraindication or intolerance.

• Endometrial cancer cohort

  1. Histologically documented, advanced (metastatic and/or unresectable) or recurrent endometrial cancer.
  2. Must have received or are intolerant to 1 but no more than 4 lines of prior systemic therapy.
  3. Must have had prior platinum and PD(L)-1 inhibitor (in same regimen or in separate regimens), if the regimen is locally available, unless there is a documented contradiction or intolerance
  4. All epithelial histologies are permitted including carcinosarcoma.

• Participants have at least one target lesion as assessed per the RECIST 1.1

• Tumor tissue from a newly obtained biopsy or archival tumor tissue is required for retrospective detection of B7 homolog 4 (B7-H4) expression by IHC in central laboratory and other biomarker analysis. Tissue from a newly obtained biopsy is preferred. If a newly obtained biopsy is not feasible, archival tumor tissue within 2 years prior to the first dose of study drug is acceptable.

• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 to 2 and no deterioration within 2 weeks before the first dose.

• Have a life expectancy of at least 12 weeks.

Exclusion criteria

• Have received any B7-H4-targeted therapy

• Have received any of cytotoxic chemotherapy drugs, anti-tumor traditional Chinese medicines or other anti-tumor drugs within 28 days prior to the first dose of study drug; or need to continue these drugs during the study.

• Have received locoregional radiation therapy within 2 weeks prior to the first dose of study drug; more than 30% of bone marrow irradiation or wide-field radiation therapy within 4 weeks prior to the first dose of study treatment.

• Presence of pleural/abdominal effusion/ascites requiring clinical intervention; presence of pericardial effusion

• Major surgery within 28 days prior to the first dose of study treatment.

• Evidence of brain metastasis unless asymptomatic;

• Has inadequate bone marrow reserve or hepatic/renal functions .

• Mean Fridericia-corrected QT interval (QTcF) QTcF >450 msec or QTcF >480 msec for participants with bundle branch blocK;

• Evidence of current clinically significant arrhythmias or ECG abnormalities

• Left ventricular ejection fraction (LVEF) < 50%.

• Have severe, uncontrolled or active cardiovascular disorders, serious or poorly controlled hypertension, clinically significant bleeding symptoms or serious arteriovenous thromboembolic events

• Has current active pneumonitis/ILD or any history of ILD, any history of pneumonitis requiring steroids or immunomodulatory treatment within 90 days of planned randomization/enrollment or any history of drug-induced pneumonitis/ILD.Have received prior therapy with topoisomerase inhibitors or topoisomerase inhibitor Antibody-drug conjugate (ADCs)

• PROC

  1. Primary platinum refractory disease defined as those who have progressed on or within 12 weeks of last dose of first line platinum therapy not permitted.
  2. Non-epithelial carcinoma, clear-cell, mucinous, germ-cell, low-grade serous, or low-grade endometrioid carcinoma not permitted.

• Endometrial cancer a. Mesenchymal tumors of the uterus (uterine sarcomas) not permitted.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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675 participants in 2 patient groups

Part 1: Dose Escalation

Experimental group

Description:

Participants with advanced solid tumors who are refractory or intolerant to established standard therapies

Treatment:

Drug: Mocertatug rezetecan

Part 2: Dose Expansion

Experimental group

Description:

Participants with platinum-resistant ovarian cancer (PROC) and endometrial cancer (EC)

Treatment:

Drug: Mocertatug rezetecan