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

Complete Trial Title:
A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of Mocertatug Rezetecan for Injection in Subjects With Advanced Solid Tumors

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

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.