Study to Evaluate D-1553 in Subjects With Solid Tumors

InventisBio

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Solid Tumor, Adult; CRC; NSCLC

Treatments: Drug: D-1553; Drug: D-1553 in combination with Drug: pembrolizumab, Drug:KEYTRUDA® , Drug: cetuximab, Drug: other

Study type: Interventional

Funder types: Industry

Identifiers

NCT04585035

KEYNOTE-C15 MK3475-C15 (Other Identifier)

D1553-101

Details and patient eligibility

About

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.

Enrollment: 180 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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180 participants in 3 patient groups

Dose escalation of D-1553 monotherapy

Experimental group

Description:

Phase 1a will evaluate up to 7 sequential cohorts with different doses of D-1553 to determine safety, tolerability, MTD and RDE in patients with solid tumors with KRasG12C mutation.

Treatment:

Drug: D-1553

Dose combination of D-1553 with other therapies

Experimental group

Description:

Phase 1b will determine the MTD of D-1553 in combination treatment in subjects with advanced or metastatic NSCLC, CRC and other solid tumors. There are multiple groups in Phase 1b for different tumor types and treatment combinations to evaluate safety, MTD and RP2D.

Treatment:

Drug: D-1553 in combination with Drug: pembrolizumab, Drug:KEYTRUDA® , Drug: cetuximab, Drug: other

Drug: D-1553

Phase 2 of D-1553 monotherapy and combination therapies

Experimental group

Description:

The Phase 2 portion is a multi-arm, parallel, open label study to evaluate the efficacy of D- 1553 single agent and combination treatments in subjects with advanced or metastatic solid tumors with KRas G12C mutation. Enrollment into phase 2 will be opened after confirmation of the recommended phase 2 dose.

Treatment:

Drug: D-1553 in combination with Drug: pembrolizumab, Drug:KEYTRUDA® , Drug: cetuximab, Drug: other

Drug: D-1553