A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Evidence of Antitumor Activity of JAB-21822 Monotherapy and Combination Therapy in Adult Patients with Advanced Solid Tumors Harboring KRAS G12C Mutation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Jacobio Pharmaceuticals Co. Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

completed 27 Dec 2024

Decision date (initial)

2024-07-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515258-25-00

EudraCT number

2021-003028-34

ClinicalTrials.gov

NCT05002270

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Dose Escalation Phase (Phase 1):
1. To evaluate the overall safety and tolerability of JAB-21822 monotherapy
2. To determine the MTD and a RP2D of JAB-21822 monotherapy administered QD in participants with relapsed or refractory solid tumors with KRAS G12C mutation

Dose Expansion Phase (Phase 2):
1. To further evaluate preliminary antitumor activity, ORR, and DOR of JAB-21822 monotherapy at the RP2D in participants with relapsed and refractory NSCLC and other solid tumors with KRAS G12C mutation, and in combination with cetuximab in mCRC with KRAS G12C mutation

Secondary objectives 5

1. Dose Escalation Phase (Phase 1): To evaluate preliminary antitumor activity of various dose levels of JAB-21822 monotherapy in participants with relapsed and refractory solid tumors with KRAS G12C mutation
2. Dose Escalation Phase (Phase 1): To characterize the PK profiles of JAB-21822 after a single dose and at steady state after multiple doses
3. Dose Expansion Phase (Phase 2): To determine PFS, OS, TTR, and DCR
4. Dose Expansion Phase (Phase 2): To further assess the overall safety and tolerability of JAB-21822 at the RP2D as monotherapy and in combination with cetuximab
5. Dose Expansion Phase (Phase 2): To further characterize the PK profiles of JAB-21822

Conditions and MedDRA coding

advanced solid tumors with KRAS G12C mutation

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participants must have at least 1 measurable lesion as defined by RECIST v1.1.
2. Participants must be able to provide an archived tumor sample
3. Participant has histologically or cytologically confirmed solid tumors with KRAS G12C mutation
4. Must have received at least 1 prior standard therapy
5. Participants must be able to swallow and retain orally administered medication.
6. Participants must have laboratory data that meet the following criteria: a. Absolute neutrophil count ≥1.5 × 109/L. b. Platelet count ≥100 × 109/L. c. Hemoglobin ≥9 g/dL. d. Albumin ≥3.0 g/dL. e. Total bilirubin ≤1.5 × ULN (with Gilbert’s syndrome, ≤2.0 × ULN). f. AST and ALT ≤1.5 × ULN (with presence of liver metastases, ≤3 × ULN). g. PT and PTT <1.5 × ULN and INR <1.5 if the participant is not on anticoagulants, or INR <3 after dose titration has been completed if the participant is on anticoagulants. h. Kidney function is normal with a CrCl ≥ 60 mL/min (measured using Cockcroft-Gault equation; see Appendix 13.4). i. TSH within normal range at baseline. Additional thyroid function testing (such as free T4, T3, etc.) can be performed at the investigator’s discretion.

Exclusion criteria 7

1. Active infection requiring systemic treatment at the start of treatment in this trial. A washout period of 7 days after the last dose of antibiotics, antivirals, or antifungals prior to first dose of study drug is required.
2. Participant has brain or spinal metastases, except if treated by surgery, surgery plus radiotherapy or radiotherapy alone, with no evidence of radiographic progression or hemorrhage for at least 28 days
3. Has active HBV or HCV
4. History of any severe and/or uncontrolled medical conditions
5. LVEF ≤50% assessed by ECHO or QTcF
6. QT interval >470 msec
7. Participants experiencing unresolved Grade >1 toxicity before the start of treatment with the study drug

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Dose Escalation Phase (Phase 1): Safety and tolerability of repeated cycles from first drug administration up to the end of the follow-up period; Incidence, nature, and severity of TEAEs, TRAEs, and death per NCI CTCAE v5
2. Dose Escalation Phase (Phase 1): Treatment-emergent changes in clinical laboratory measurements, ECG findings, vital signs, ECOG performance status, and physical examination findings
3. Dose Escalation Phase (Phase 1): Number and proportion of participants who experience at least 1 DLT during the first 21 days of treatment
4. Dose Expansion Phase (Phase 2): ORR defined as the percentage of participants with PR or CR based on RECIST v1.1
5. Dose Expansion Phase (Phase 2): DOR

Secondary endpoints 9

1. Dose Escalation Phase (Phase 1): ORR defined as the percentage of participants with PR or CR based on RECIST v1.1
2. Dose Escalation Phase (Phase 1): DCR, TTR, DOR, and PFS
3. Dose Escalation Phase (Phase 1): PK parameters of JAB-21822 including, but not limited to, Cmax, tmax, Ctrough, AUC0-τ, AUC0-t, AUC0 inf, t½, CL/F, Vz/F, Rac Cmax, and Rac AUC
4. Dose Expansion Phase (Phase 2): PFS and TTR
5. Dose Expansion Phase (Phase 2): OS
6. Dose Expansion Phase (Phase 2): DCR
7. Dose Expansion Phase (Phase 2): Safety and tolerability of repeated cycles from first drug administration up to the end of the follow-up period; Incidence, nature, and severity of TEAEs, TRAEs, and death per NCI CTCAE v5
8. Dose Expansion Phase (Phase 2): Treatment-emergent changes in clinical laboratory measurements, ECG findings, vital signs, ECOG performance status, and physical examination findings
9. Dose Expansion Phase (Phase 2): PK parameters of JAB-21822 and potential factors (covariates) that impact the PK parameters

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Jacobio Pharmaceuticals Co. Ltd.

Sponsor organisation

Jacobio Pharmaceuticals Co. Ltd.

Address

Bld 8, No 105 Jinghai 3rd Road Bda No 105 Jinghai 3rd Road Bda

City

Beijing

Postcode

100176

Country

China

Scientific contact point

Organisation

Jacobio Pharmaceuticals Co. Ltd.

Contact name

Zheng Xu

Public contact point

Organisation

Jacobio Pharmaceuticals Co. Ltd.

Contact name

Zheng Xu

Third parties 1

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications