Tuvusertib (M1774) in Combination with Cemiplimab in Participants with Non-Squamous NSCLC (DDRiver NSCLC 322)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Healthcare KGaA

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

20 Dec 2023 → ongoing

Decision date (initial)

2023-11-29

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Healthcare KGaA

External identifiers

EU CT number

2022-502010-85-00

ClinicalTrials.gov

NCT05882734

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacogenomic, Pharmacokinetic, Dose response, Others, Pharmacogenetic

1. Phase 1b: To assess efficacy in terms of objective response (OR), safety, and tolerability of interventions of Tuvusertib in combination with cemiplimab, to support selection of a dosing regimen for the Phase 2a part
2. Phase 1b: To evaluate the safety and tolerability of Tuvusertib in combination with cemiplimab to support selection of dosing regimen for Phase 2a
3. Phase 2a: To assess efficacy of intervention in terms of OR with Tuvusertib in combination with cemiplimab

Secondary objectives 7

1. Phase 1b: To assess efficacy in terms of DoR of Tuvusertib in combination with cemiplimab
2. Phase 1b: To assess efficacy in terms of PFS with Tuvusertib in combination with cemiplimab irrespective of subsequent anticancer therapy
3. Phase 1b: To assess efficacy in terms of OS with Tuvusertib in combination with cemiplimab followed by subsequent anticancer therapy
4. Phase 2a: To assess efficacy in terms of DoR of Tuvusertib in combination with cemiplimab
5. Phase 2a: To assess efficacy in terms of PFS with Tuvusertib in combination with cemiplimab irrespective of subsequent anticancer therapy
6. Phase 2a: To assess efficacy in terms of OS with Tuvusertib in combination with cemiplimab followed by subsequent anticancer therapy
7. Phase 2a: To evaluate the safety and tolerability of Tuvusertib in combination with cemiplimab

Conditions and MedDRA coding

Non-Squamous Non-Small Cell Lung Cancer

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

IPD plan description

We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Are ≥ 18 years of age at the time of signing the informed consent
2. Are diagnosed with nsqNSCLC histologically or cytologically confirmed
3. Radiologically confirmed/documented disease progression during or after the following systemic therapies (all required): •a. At most, 1 line of anti-PD-(L)1 therapy for locally advanced or metastatic disease. Note 1: Rechallenge with the same anti-PD-(L)1 for disease considered sensitive to anti-PD-(L)1 therapy (e.g. after a treatment break) is considered 1 line. Note 2: this includes (neo)adjuvant anti-PD-(L)1 therapy for locally advanced disease, provided disease progression occurs within 16 weeks of the last dose of anti-PD-(L)1 therapy. •b. Platinum-based therapy for locally advanced or metastatic disease, given in combination or sequentially with anti-PD-(L)1 therapy. Participants who received (neo)adjuvant platinum-based therapy meet this criterion if disease progression occurred within 6 months from the last dose that the participant received that therapy. No additional cytotoxic therapies after progression on platinum-based therapy are allowed •c. Prior best overall response of stable disease or better with anti-PD-(L)1 therapy •d. Disease progression must have occurred while the participant has been receiving anti-PD-(L)1 therapy or within 16 weeks of the last dose of anti-PD-(L)1 therapy
4. Measurable disease per RECIST v1.1, as assessed by the Investigator
5. ECOG PS 0 or 1
6. Adequate hematological, hepatic and renal function as defined in the protocol.
7. Archival FFPE tumor tissue is available or tumor genomic profiling with a NGS based test performed in a certified laboratory and PD-L1 status as determined by an assay of appropriate regulatory status are required.
8. Phase 2a part only: central liquid biopsy analysis of tumor molecular alterations with an assay with appropriate regulatory status. Participants will be allocated to Stratum A, B and C as defined in the protocol.
9. Other protocol defined inclusion criteria could apply

Exclusion criteria 5

1. Participants with tumors harboring actionable EGFR or ALK genomic aberrations. Participants with tumors with other actionable aberrations are eligible and allowed to have received up to 1 line of available targeted therapy
2. History of additional malignancy within 3 years before the date of enrollment. Exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the Investigator, with concurrence of the Sponsor’s Medical Monitor, is considered cured with minimal risk of recurrence within 3 years
3. Known brain metastases, unless clinically stable
4. history of (noninfectious) pneumonitis that required systemic corticosteroids or current pneumonitis/interstitial lung disease
5. Other protocol defined inclusion criteria could apply.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase 1b/Phase 2a: Confirmed Overall response (OR) According to Response Evaluation Criteria in Solid Tumor (RECIST) 1.1 As assessed by Investigator
2. Phase 1b: Number of Participants With Adverse Events (AEs) and Treatment- related AEs

Secondary endpoints 4

1. Phase 1b/Phase 2a: Duration of Response (DoR) According to RECIST 1.1 as Assessed by the Investigator
2. Phase 1b/Phase 2a: Progression Free Survival (PFS) According to RECIST 1.1 as Assessed by the Investigator
3. Phase 1b/Phase 2a: Overall survival (OS)
4. Phase 2a: Number of Participants With AEs and Treatment-related AEs

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Healthcare KGaA

Sponsor organisation

Merck Healthcare KGaA

Address

Frankfurter Strasse 250

City

Darmstadt

Postcode

64293

Country

Germany

Scientific contact point

Organisation

Merck Healthcare KGaA

Contact name

Global Regulatory Affairs

Public contact point

Organisation

Merck Healthcare KGaA

Contact name

Global Regulatory Affairs

Third parties 12

Locations

5 EU/EEA countries · 42 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 31 files

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

Application history

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