Clinical trial NCT04585035: Study to Evaluate D-1553 in Subjects With Solid Tumors
Official title: A Phase 1/2, Open Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of D-1553 in Subjects With Advanced or Metastatic Solid Tumors With KRasG12C Mutation
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor, Adult
NSCLC
CRC
Lead sponsor: InventisBio Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2020-10-14
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase Ia dose escalation portion of the study followed by a Phase Ib dose combination portion. Phase 2 will consist of 5 treatment arms.
Primary purpose: TREATMENT

Brief summary: This is a phase 1/2, open label study of D-1553 single agent and combination treatment to assess the safety and tolerability, identify the MTD and RP2D, evaluate the PK properties and antitumor activities in subjects with advanced or metastatic solid tumor with KRasG12C mutation.


Eligibility criteria: Inclusion criteria

* Subject with histologically proven, locally advanced, unresectable and/or metastatic solid tumor, for which no standard treatment is available, or the subject is refractory to or intolerant of existing standard treatment.
* Subject has KRasG12C mutation in tumor tissue or other bio-specimens containing cancer cells or DNA. Historical, local laboratory result (up to 5 years prior to this study) can be used for Phase 1 subjects. Phase 2 subjects must be tested for KRasG12C mutation by a central laboratory.
* Subject has tumor type requirement as follows: advanced or metastatic solid tumors including NSCLC and CRC.
* Subject has measurable disease according to RECIST, v1.1.

Exclusion Criteria:

* Subject with unstable or progressive central nervous system (CNS) metastases.
* Subject with acute myocardial infarction, severe/unstable angina; or with cardiac insufficiency of New York Heart Association Functional Classification Grade 2 or above.
* Subject has corrected QT interval using Fridericia's formula (QTcF) prolongation at rest, where the mean QTc interval is \> 480 msec based on triplicate measurements of electrocardiogram (ECG).
* Subject with stroke or other severe cerebrovascular diseases within 12 months before enrollment;
* Subject with interstitial lung disease or acute lung infection not yet recovered including but not limited to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection;
* Subject has any history or evidence of substance abuse or medical, psychological or social conditions that may, in the opinion of the investigator, interfere with participation in the study or evaluation of the study results.
* Subject has impaired gastrointestinal (GI) function or GI diseases that may significantly alter the absorption or metabolism of oral medications.
* Subject has unresolved toxicities from prior anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI CTCAE, v5.0, Grade ≤ 1 (Grade ≤ 2 for peripheral neuropathy).
* Subject had major surgery within 4 weeks prior to study intervention administration or last dose of palliative radiation therapy within 2 weeks prior to study intervention administration.
* Subject is pregnant or lactating.

Primary outcomes:
measure: Subject incidence of Dose-limiting toxicities (DLT)
timeFrame: through out the DLT period, approximately 21 days
measure: Number of subjects participants with adverse events
timeFrame: Through study completion, approximately 3 years
measure: Plasma concentration of D-1553 as a single agent or in combination with other therapies in subjects wiht advanced or metastatic solid tumors with KRas G12C mutation.
timeFrame: Through study completion, approximately 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Fresno
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: New York
country: United States
facility: Research Site
state: New York
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Blacktown
country: Australia
facility: Research Site
state: New South Wales
city: East Albury
country: Australia
facility: Research Site
state: New South Wales
city: Kogarah
country: Australia
facility: Research Site
state: New South Wales
city: Waratah
country: Australia
facility: Research Site
state: New South Wales
city: Woodville South
country: Australia
facility: Research Site
state: South Australia
city: Fitzroy
country: Australia
facility: Research Site
state: Victoria
city: Frankston
country: Australia
facility: Research Site
state: Victoria
city: Malvern
country: Australia
facility: Research Site
state: Victoria
city: Nedlands
country: Australia
facility: Research Site
state: Western Australia
city: Seogu
country: Korea, Republic of
facility: Research Site
state: Busan
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
state: Gyeonggi-Do
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Tainan
country: Taiwan
facility: Research Site
city: Taipei City
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan City
country: Taiwan
facility: Research Site
Study officials:
References: