A Phase 1/2a Study of DB-1311/BNT324 in Advanced/Metastatic Solid Tumors

Exclusion Criteria

• •* Has received 1 or 2 prior systemic therapy regimens for recurrent or metastatic disease;
• •* Has experienced disease progression during or after treatment with an anti-PD-1/L1 agent administered either as monotherapy or in combination.
• •Note: Subjects basically should receive prior standard therapy.
• •• However, if the investigator judges the therapy is not appropriate for the subject, the prior standard therapy is not necessarily mandated for the eligibility.
• •• Has a Child-Pugh class A liver score within 7 days of first dose of study drug.
• •20. Cervical cancer subjects (Phase 2a Cohort 7 ONLY) • Has recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or adenosquamous histology, and:
• •• Has experienced disease progression during or after treatment with a standard of care systemic chemotherapy doublet, or platinum-based therapy (if eligible), defined as either: d. paclitaxel + cisplatin + bevacizumab + anti-PD-(L)1 agent, or e. paclitaxel + carboplatin + bevacizumab + anti-PD-(L)1 agent, or f. paclitaxel + topotecan + bevacizumab + anti-PD-(L)1 agent Note: In cases where bevacizumab and/or anti-PD-(L)1 agent is not a standard of care therapy or the subject was ineligible for such treatment according to local standards, prior treatment with bevacizumab and/or anti-PD-(L)1 agent is not required.
• •• Has received 1 or 2 prior systemic therapy regimens for recurrent or metastatic cervical cancer. Chemotherapy administered in the adjuvant or neoadjuvant setting, or in combination with radiation therapy, should not be counted as a systemic therapy regimen. Single agent therapy with an anti-PD(L)1 agent for recurrent or metastatic cervical cancer should be counted.
• •21. Subjects with other solid tumors (Phase 2a Cohort 8 ONLY) • Histologically or cytologically confirmed solid tumors. • Progressed or relapsed after at least one prior standard therapeutic regimen (Patients who have not received all approved or standard treatments for their cancer must be informed that these alternatives to receiving DB-1311/BNT324 are available prior to consenting to participate in this trial).
• •22. HNSCC subjects (Phase 2a Cohort 9 and Cohort 13)
• •• Histologically or cytologically confirmed refractory/metastatic (R/M) HNSCC (not including NPC) that is considered incurable by local therapies.
• •• Progressed on or after prior standard therapeutic regimen.
• •23. Subjects with rare tumors (Phase 2a Cohort 10 ONLY) Histologically or cytologically confirmed rare tumor types. Progressed or relapsed after at least one prior standard therapeutic regimen (Patients who have not received all approved or standard treatments for their cancer must be informed that these alternatives to receiving DB-1311/BNT324 are available prior to consenting to participate in this trial).
• •24. Post lutetium-177 CRPC subjects (Phase 2a Cohort 11 ONLY):
• •Pathologically documented metastatic adenocarcinoma of the prostate cancer. Progressive metastatic CRPC as defined: 1) castrate levels of serum testosterone \< 50 ng/dL AND 2) progressive disease as defined by PCWG3 criteria.
• •25. Taxane-naive CRPC subjects (Phase 2a Cohort 12, 16, 17 ONLY)
• •* Pathologically documented metastatic adenocarcinoma of the prostate cancer. Progressive metastatic CRPC as defined: 1) castrate levels of serum testosterone \< 50 ng/dL AND 2) progressive disease as defined by PCWG3 criteria.
• •26, PROC subjects (Phase 2a Cohort 14 ONLY)
• •* Subjects must have a confirmed diagnosis of OC, primary peritoneal cancer, or fallopian tube cancer, all of which with high-grade serous or endometrioid histology..
• •* Subjects must have platinum-resistant disease:
• •* Received at least 1 but ≤ 3 lines of prior systemic anticancer therapy and have radiographic progressed on or after their most recent line of therapy.
• •27\. CSPC with suboptimal PSA response (Phase 2a Cohort 18 ONLY)
• •Pathologically documented adenocarcinoma of the prostate cancer.
• •Having advanced/unresectable, or metastatic disease and confirmed by imaging (e.g., CT and/or bone scan).
• •Having received ADT and enzalutamide or abiraterone for ≥4 months, with suboptimal PSA response.
• •1. Prior treatment with B7-H3 targeted therapy.
• •2. Prior treatment with antibody drug conjugate with topoisomerase inhibitor (e.g., trastuzumab deruxtecan).
• •3. Has a medical history of symptomatic congestive heart failure (CHF) (New York Heart Association \[NYHA\] classes II-IV) or serious cardiac arrhythmia requiring treatment.
• •4. Has a medical history of myocardial infarction or unstable angina within 6 months before enrollment.
• •5. Has an average of Fredericia's formula-QT corrected interval (QTcF) prolongation to \> 470 millisecond (ms) in males and females based on a 12-lead electrocardiogram (ECG) in triplicate.
• •6. Use of concomitant medications known to prolong the QT interval. If the use is deemed necessary, they should be administered with caution and closely monitoring the QT interval, after discussed with the Sponsor.
• •7. Has a medical history of interstitial lung diseases (e.g., non-infectious interstitial pneumonia, pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or current interstitial lung diseases or who are suspected to have these diseases by imaging at screening.
• •8. Has a history of underlying pulmonary disorder including, but not limited to, pulmonary emboli within 3 months of the start of study treatment, severe asthma, severe COPD, restrictive lung disease, and other clinically significant pulmonary compromise or requirement for supplemental oxygen.
• •9. Clinically significant gastrointestinal disorder including, but not limited to, history of gastrointestinal fistulation that need long-term intravenous nutrition; gastrointestinal dysfunction that need long-term enteral nutrition through the tube feeding; gastrointestinal obstruction/perforation that not recovered within 6 months prior to the enrollment.
• •10. Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk of bleeding; A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment (Only applicable to HCC patients).
• •11. Metastatic disease that involves major airways or blood vessels (e.g., patients with vascular invasion of the major portal vein and inferior vena cava).
• •12. Clinically uncontrolled pleural effusion, ascites or pericardial effusion requiring drainage, peritoneal shunt or cell-free concentrated ascites reinfusion therapy within 2 weeks prior to the enrollment.
• •13. Any autoimmune, connective tissue or inflammatory disorders (e.g., rheumatoid arthritis, Sjögren's, sarcoidosis) where there is documented, or a suspicion of pulmonary involvement at the time of screening.
• •14. Has an uncontrolled infection requiring intravenous injection of antibiotics, antivirals, or antifungals.
• •15. Know human immunodeficiency virus (HIV) infection.
• •16. Subjects have active viral (any etiology) hepatitis are excluded. However, subjects with serologic evidence of chronic hepatitis B virus (HBV) infection (defined by a positive hepatitis B surface antigen \[HBsAg\] test or a positive hepatitis B core antibody test) who have a viral load below the limit quantification (e.g., HBV DNA titer \< 1000 cps/mL or 200 IU/mL) and are willing to and maintain antiviral treatment if required, are eligible. However, subjects with a history of hepatitis C virus (HCV) infection who have completed curative antiviral treatment and have a viral load below the limit of quantification are eligible for study entry.
• •17. Is a lactating mother (women who are willing to temporarily interrupt breastfeeding will also be excluded), or pregnant as confirmed by pregnancy tests performed within 7 days prior to enrollment.
• •18. Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study randomization.
• •19. Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE version 5.0, grade ≤ 1 or baseline. Subjects with chronic Grade 2 toxicities (e.g., Grade 2 neuropathy) may be eligible based on the discussion and agreement between Investigator and Sponsor.
• •20. Has multiple primary malignancies within 3 years before enrollment, except adequately resected non-melanoma skin cancer (e.g., resected basal or squamous cell skin cancer), curatively treated in-situ disease (e.g., carcinoma in situ of the cervix or breast), other solid tumors curatively treated (e.g., superficial bladder cancer), or contralateral breast cancer.
• •21. Has substance abuse or any other medical conditions that would increase the safety risk to the subject or interfere with participation or evaluation of the clinical study in the opinion of the investigator.
• •22. Has known hypersensitivity to either the drug substances or inactive ingredients in the drug product.
• •23. Patients with other reasons that, in the opinion of the Investigator, make them unsuitable to participate in this study.