A study of sigvotatug vedotin versus docetaxel in previously treated non-small cell lung cancer (Be6A Lung-01)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Seagen Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 Feb 2024 → ongoing

Decision date (initial)

2024-04-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Seagen Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Efficacy, Safety, Therapy, Pharmacodynamic

• To compare the overall survival (OS) between the experimental arm (sigvotatug vedotin) and control (docetaxel) arms in all participants and in the IB6-high subgroup
• To compare the progression free survival (PFS) as assessed by blinded independent central review (BICR) between the experimental and control arms in all participants and in the IB6-high subgroup

Secondary objectives 7

1. To compare the objective response rate (ORR) as assessed by BICR between the experimental and control arms in all participants and in the IB6-high subgroup
2. To compare the ORR as assessed by investigator between the experimental and control arms
3. To compare the PFS as assessed by investigator between the experimental and control arms
4. To estimate the duration of response (DOR) for the experimental and control arms
5. To characterize the safety and tolerability profile of sigvotatug vedotin
6. To compare change in quality of life (QoL), functioning, and lung cancer symptom response between the experimental and control arms
7. To compare time to deterioration (TTD) in QoL, functioning, and lung cancer symptoms between the experimental and control arms

Conditions and MedDRA coding

Non-Small Cell Lung Cancer (NSCLC)

Regulatory references

Plan to share IPD

Yes

IPD plan description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Histologically or cytologically confirmed diagnosis of locally advanced, unresectable (Stage IIIB, IIIC), or metastatic (Stage IV: M1a, M1b, or M1c) NSCLC per the American Joint Committee on Cancer (AJCC) Staging Manual, Version 8.0, and the Union for International Cancer Control (UICC) Staging System (Eighth edition).
2. Participants must have NSCLC with nonsquamous histology: oTumors with squamous, or predominantly squamous histology are excluded. oTumors with small cell elements are excluded
3. Participants must have received the following prior therapies and progressed during or relapsed after receiving their most recent prior therapy: • Participants with no known AGAs must fulfill 1 of the following conditions: o Received a platinum based combination therapy for the treatment of metastatic or recurrent disease and a PD-(L)1 monoclonal antibody (concurrently or sequentially with platinum-based chemotherapy), unless contraindicated. o Experienced disease progression within 6 months of the last dose of platinum-based chemotherapy in the adjuvant, neoadjuvant, or chemoradiotherapy setting and received a PD-(L)1 monoclonal antibody at any time during the course of treatment. • Participants with known AGAs (eg, EGFR mutations, ALK translocations, or other relevant actionable mutations) must fulfill the following conditions: o Must have received at least 1 relevant AGA-targeted therapy and, in the opinion of the investigator, additional AGA-targeted therapy is not in the best interest of the participant. o Received a platinum-based combination therapy for the treatment of metastatic or recurrent disease, or experienced disease progression within 6 months of the last dose of platinum-based chemotherapy in the adjuvant, neoadjuvant, or chemoradiotherapy setting. o May have received up to 1 PD-(L)1 monoclonal antibody (concurrently or sequentially with platinum-based chemotherapy).
4. Measurable disease based on RECIST v1.1, as determined by investigator.

Exclusion criteria 4

1. Prior therapy: • Prior treatment with antimicrotubule agents (taxanes, vinca alkaloids, or MMAEs) in the locally advanced, unresectable/refractory, or metastatic setting. - Prior antimicrotubule agent exposure in curative settings (including adjuvant, neoadjuvant, or chemoradiotherapy) is permissible. • Received more than 1 prior line of cytotoxic chemotherapy in the locally advanced, unresectable/refractory, or metastatic setting. - Prior cytotoxic chemotherapy in curative settings is permissible. • At least 14 days must have elapsed from the last dose of radiotherapy until Cycle 1 Day 1. Participants must have recovered from all radiation related toxicities that would otherwise prevent trial participation. Palliative radiotherapy within the 14 days prior to Cycle 1 Day 1 may be allowed upon discussion with the sponsor’s medical monitor or their designee. • Prior radiation therapy to the lung parenchyma that is >30 Gray (Gy) within 6 months of Cycle 1 Day 1. • Any systemic anticancer therapy (standard or experimental) within 21 days prior to Cycle 1 Day 1. • Participants with Grade ≥2 ongoing toxicities associated with prior therapies will be excluded, with the exception of alopecia.
2. Pre-existing peripheral neuropathy Grade ≥2 per NCI CTCAE v5.0.
3. Uncontrolled diabetes mellitus, defined as HbA1c ≥8.0% or HbA1c between 7% and <8.0% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
4. Participants with any of the following respiratory conditions: • Evidence of noninfectious ILD or pneumonitis that: o Was previously diagnosed and required systemic steroids, or o Is currently diagnosed and managed, or o Is suspected on radiologic imaging at screening • Known DLCO (adjusted for hemoglobin) <50% predicted • Any Grade ≥3 pulmonary disease unrelated to underlying malignancy including, but not limited to: o Pulmonary emboli within 3 months of Cycle 1 Day 1 o Severe asthma requiring systemic corticosteroids within 30 days prior to Cycle 1 Day 1 or is not well controlled with low-dose inhaled corticosteroids/long-acting beta-2 agonists o Severe chronic obstructive pulmonary disease requiring supplemental oxygen or systemic corticosteroids o Any autoimmune or inflammatory disorders with significant pulmonary parenchymal involvement at time of screening (ie, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. OS
2. PFS using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) as assessed by BICR

Secondary endpoints 12

1. Confirmed ORR using RECIST v1.1 as assessed by BICR
2. Confirmed ORR using RECIST v1.1 as assessed by investigator
3. PFS using RECIST v1.1 as assessed by investigator
4. DOR using RECIST v1.1 as assessed by BICR
5. DOR using RECIST v1.1 as assessed by investigator
6. Type, incidence, severity, seriousness, and relatedness of adverse events (AEs)
7. Mean scores and change from baseline in the global health status/QoL combined score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
8. Mean scores and change from baseline in physical functioning and role functioning scores on the EORTC QLQ-C30
9. Mean scores and change from baseline in the dyspnea, cough, and chest pain scores on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC13)
10. TTD in the global health status/QoL combined score on the EORTC QLQ-C30
11. TTD in physical functioning and role functioning scores on the EORTC QLQ-C30
12. TTD in the dyspnea, cough, and chest pain scores on the EORTC QLQ-LC13

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Seagen Inc.

Sponsor organisation

Seagen Inc.

Address

21823 30th Drive Southeast

City

Bothell

Postcode

98021-3907

Country

United States

Scientific contact point

Organisation

Seagen Inc.

Contact name

Scott Knowles

Public contact point

Organisation

Seagen Inc.

Contact name

Scott Knowles

Third parties 26

Locations

13 EU/EEA countries · 100 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

Serious breaches 1 · Art. 52 CTR

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 236 files

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

Application history

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