Study to Evaluate D-1553 in Subjects With Solid Tumors

Sponsor

InventisBio Co., Ltd (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04585035

Collaborator

Merck Sharp & Dohme LLC (Industry)

200

Enrollment

Locations

Arms

Anticipated Duration (Months)

7.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor, Adult NSCLC CRC	Drug: D-1553 Drug: Other	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

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.Phase Ia dose escalation portion of the study followed by a Phase Ib dose combination portion. Phase 2 will consist of 5 treatment arms.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 2, 2020

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose escalation of D-1553 monotherapy 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.	Drug: D-1553 D-1553 is a novel, targeted KRasG12C inhibitor that is being developed as a potential oral agent for advanced or metastatic solid tumors with KRasG12C mutation.
Experimental: Dose combination of D-1553 with other therapies 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.	Drug: D-1553 D-1553 is a novel, targeted KRasG12C inhibitor that is being developed as a potential oral agent for advanced or metastatic solid tumors with KRasG12C mutation. Drug: Other Standard treatment of solid tumor, NSCLC or CRC
Experimental: Phase 2 of D-1553 monotherapy and combination therapies 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.	Drug: D-1553 D-1553 is a novel, targeted KRasG12C inhibitor that is being developed as a potential oral agent for advanced or metastatic solid tumors with KRasG12C mutation. Drug: Other Standard treatment of solid tumor, NSCLC or CRC

Arm

Intervention/Treatment

Experimental: Dose escalation of D-1553 monotherapy

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.

Drug: D-1553

D-1553 is a novel, targeted KRasG12C inhibitor that is being developed as a potential oral agent for advanced or metastatic solid tumors with KRasG12C mutation.

Experimental: Dose combination of D-1553 with other therapies

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.

Drug: D-1553

D-1553 is a novel, targeted KRasG12C inhibitor that is being developed as a potential oral agent for advanced or metastatic solid tumors with KRasG12C mutation.

Drug: Other

Standard treatment of solid tumor, NSCLC or CRC

Experimental: Phase 2 of D-1553 monotherapy and combination therapies

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.

Drug: D-1553

D-1553 is a novel, targeted KRasG12C inhibitor that is being developed as a potential oral agent for advanced or metastatic solid tumors with KRasG12C mutation.

Drug: Other

Standard treatment of solid tumor, NSCLC or CRC

Outcome Measures

Primary Outcome Measures

Subject incidence of Dose-limiting toxicities (DLT) [through out the DLT period, approximately 21 days]
Number of subjects participants with adverse events [Through study completion, approximately 3 years]
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. [Through study completion, approximately 3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 biospecimens 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Fresno	California	United States	93720
2	Research Site	Orange	California	United States	92868
3	Research Site	San Francisco	California	United States	94158
4	Research Site	Louisville	Kentucky	United States	40202
5	Research Site	Detroit	Michigan	United States	48202
6	Research Site	New York	New York	United States	11432
7	Research Site	Portland	Oregon	United States	97213
8	Research Site	Pittsburgh	Pennsylvania	United States	15232
9	Research Site	Blacktown	New South Wales	Australia	2148
10	Research Site	East Albury	New South Wales	Australia	2640
11	Research Site	Kogarah	New South Wales	Australia	2217
12	Research Site	Waratah	New South Wales	Australia	2298
13	Research Site	Woodville South	South Australia	Australia	5011
14	Research Site	Fitzroy	Victoria	Australia	3065
15	Research Site	Frankston	Victoria	Australia	3199
16	Research Site	Malvern	Victoria	Australia	3144
17	Research Site	Nedlands	Western Australia	Australia	6009
18	Research Site	Seo-Gu	Busan	Korea, Republic of	602-715
19	Research Site	Seongnam-si	Gyeonggi-Do	Korea, Republic of	463-707
20	Research Site	Seocho-Gu	Seoul	Korea, Republic of	06591
21	Research Site	Songpa-Gu	Seoul	Korea, Republic of	138-736
22	Research Site	Seoul		Korea, Republic of	152-703
23	Research Site	Tainan		Taiwan	704
24	Research Site	Taipei City		Taiwan	10002
25	Research Site	Taipei		Taiwan	11217
26	Research Site	Taoyuan City		Taiwan	333

Sponsors and Collaborators

InventisBio Co., Ltd
Merck Sharp & Dohme LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

InventisBio Co., Ltd

ClinicalTrials.gov Identifier:

NCT04585035

Other Study ID Numbers:

D1553-101
KEYNOTE-C15

First Posted:

Oct 14, 2020

Last Update Posted:

Mar 29, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Neoplasms

Study Results

No Results Posted as of Mar 29, 2022