A Phase Ib/II Trial of HS-20110 Combination Therapies in Advanced Colorectal Cancer Patients.

Official title

A Phase Ib/II Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-20110 Combination Therapies in Patients With Advanced Colorectal Cancer.

Overview

This is a multicenter, open-label Phase Ib/II clinical study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of the HS-20110 combination therapies in Patients with Advanced Colorectal Cancer. "Rolling 6" design would be used to conduct dose escalation part of this study. This study consists of phase Ib and phase II. After RP2D was determined in phase Ib, then a phase II study will be conducted to further evaluate the efficacy, safety, tolerability, and PK of the HS-20110 combination therapies in Patients with mCRC.

Interventions

• Drug Cohort 1: HS-20110+ Bevacizumab+5-FU/leucovorin
  HS-20110 for IV infusion of various dosage in combination with Bevacizumab+5-FU/leucovorin administered in Q2W doseing cycles
• Drug Cohort 2: HS-20110+Bevacizumab+Oxaliplatin+5-FU/leucovorin
  HS-20110 for IV infusion of various dosage in combination with Bevacizumab+Oxaliplatin+5-FU/leucovorin administered in Q2W doseing cycles
• Drug Cohort 3: HS-20110+Bevacizumab+Oxaliplatin+Capecitabine
  HS-20110 for IV infusion of various dosage in combination with Bevacizumab+Oxaliplatin+Capecitabine administered in Q3W doseing cycles

Primary outcome measures

• Maximum tolerated dose (MTD) or maximum applicable dose (MAD) [Time frame: From day 1 to one month after the last dose in Phase 1b]
• Recommended phase 2 dose (RP2D) [Time frame: From day 1 to one month after the last dose in Phase 1b]
• Objective response rate (ORR) as per RECIST v1.1 [Time frame: From day 1 to 3 months after the last patient enrolled in Phase 2]

Secondary outcome measures (8)

• Incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to dose modification or permanent discontinuation, and specific laboratory abnormalities [Time frame: From the first dose until 90 days after the last dose]
• Objective response rate (ORR) [Time frame: From first dose until 3 years after last dose]
• Incidence of anti-HS-20110 antibody (ADA) [Time frame: From the first dose until 90 days after the last dose]
• Drug concentrations of the three components of HS-20110 (including antibody-drug conjugates, total antibody, and payload) [Time frame: From the first dose until 90 days after the last dose]
• disease control rate (DCR) [Time frame: From first dose until 3 years after last dose]
• duration of response (DoR) [Time frame: From first dose until 3 years after last dose]
• progression-free survival (PFS) [Time frame: From first dose until 3 years after last dose]
• overall survival (OS) [Time frame: From first dose until 3 years after last dose]

Eligibility criteria

Inclusion criteria

• Males or females, aged ≥ 18 years.
• Participants with pathologically confirmed advanced Colorectal Cancer.
• Participants have at least 1 target lesion other than CNS lesions according to RECIST 1.1.
• MSI was tested to be non-MSI-H, and without BRAF V600E mutation.

Exclusion criteria

• Participants have received or are receiving the following treatment:

• Anti-tumor drugs within 14 days prior to the first dose of study treatment; any other IMPs or macromolecular anti-tumor drugs within 28 days prior to the first dose of study treatment.
• Local radiotherapy within 2 weeks prior to the first dose of study treatment; irradiation of more than 30% of bone marrow or extensive radiotherapy within 4 weeks prior to the first dose of study treatment.
• Major surgery within 4 weeks prior to the first dose of study treatment.
• Participants previously treated with drugs that are moderate to strong inhibitors or moderate to strong inducers of cytochrome P450 (CYP) 3A4, strong inhibitors or strong inducers of CYP2D6, P-glycoprotein (P-gp), breast cancer resistance protein (BCRP) or drugs with a narrow therapeutic range that are sensitive substrates of P-gp or BCRP within 7 days prior to the first dose of the IMP. Participants who need to receive these drugs during the study period should also be excluded.
• Current use of drugs known to prolong the QT interval or that may cause torsade de pointes. Participants who need to receive these drugs during the study period should also be excluded.
• Live vaccine or live-attenuated vaccine within 28 weeks prior to the first dose.
• Participants who have any Grade ≥ 2 residual toxicity according to Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) from prior therapies (except alopecia and residual neurotoxicity).
• Inadequate bone marrow reserve or hepatic and renal functions.
• Participants with a history of severe allergy (such as anaphylactic shock), previous severe infusion reactions, or allergy to recombinant human or murine proteins.
• Participants who are allergic to any component of HS-20110 combination therapies.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT07283367 · HS-20110-102

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗