Phase 1/2 dose escalation and cohort expansion study evaluating MCLA-158 (Petosemtamab) as single agent or in combination in advanced solid tumors

Phase 1

• Conditions: Metastatic colorectal cancerAdvanced solid tumors; MedDRA version: 27.0Level: PTClassification code 10052358Term: Colorectal cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: LLTClassification code 10065147Term: Malignant solid tumorSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-004745-24-NL
• Lead Sponsor: Merus N.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-04-19
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 567

Inclusion Criteria

1 Signed ICF
2 Age = 18 y
3. Histologically/cytologically confirmed solid tumors with evidence of
metastatic or locally advanced disease not amenable to standard therapy
with curative intent:
• Expansion cohorts: patients (pts) with locally advanced unresectable
or metastatic disease for the following indications:
oSINGLE AGENT
o2nd/3rd-LINE HNSCC PATIENTS: pts who have progressed on or after,
or are intolerant to, anti-PD-(L)1 therapy as monotherapy or in
combination , and have progressed to a Pt-based chemotherapy less
than 6 months from the last Pt dose, with no previous EGFR inhibitors.
Pts with no more than 2 prior lines of treatment in recurrent or
metastatic disease not amenable to standard therapy with curative
intent.
HPV status by p16 IHC or molecular HPV test for all oropharyngeal
tumors should be reported when available.
The eligible HNSCC primary tumor locations are oropharynx, oral cavity,
hypopharynx, and larynx.
oCancers of the anogenital tract with squamous cell histology
oSkin SCC
oNSCLC non-SCC and SCC
oGEA with histologically confirmed EGFR amplification FISH score
EGFR/CEP7 ratio =2.0, or NGS EGFR copy =8, or cfDNA =2.5, or EGFR
IHC H-score =200)
oPA
o mCRC in 3L+. Patients should be free of mutations in RAS, KRAS,
NRAS, HRAS, RAF, BRAF, ARAF, RAF1,
If the patient was treated with an EGFR inhibitor in 1L or 2L, then the
patient should have shown CR)/PR and should have at least 6 months of
interval since the last administration of EGFR inhibitor.
oCOMBINATION
o1st HNSCC: pts eligible to receive pembro. as 1st-line monotherapy
with tumors expressing PD-L1, CPS =1; pts should not have previous
systemic therapy in the
recurrent or metastatic setting, although previous systemic therapy as
part of multimodal treatment for locally advanced disease is allowed if
ended =6 months prior to signing the ICF. The eligible HNSCC primary
tumor locations are oropharynx, oral cavity, hypopharynx, and larynx.
Previous treatments with anti-PD-(L)1 or anti-EGFR therapies are not
allowed
2L mCRC: Patients should have been previously diagnosed with
histologically or cytologically confirmed unresectable or metastatic
adenocarcinoma of the CRC. Patients must be RAS/RAF WT . Patients
must be naive to prior anti-EGFR . Radiographically confirmed disease
progression must have occurred within 6 months of prior 1L.
o Cohort petosemtamab and FOLFIRI: patients should have had only 1
prior chemotherapy regimen for the metastatic setting, consisting of 1L
fluoropyrimidine-oxaliplatin-based chemotherapy ± bevacizumab. Note:
FOLFOX-based adjuvant treatment would be considered front-line if PD
occurred within 6 months of completion of adjuvant therapy.
o Cohort petosemtamab and FOLFOX: patients should have had only 1
prior chemotherapy regimen for the metastatic setting, consisting of 1L
fluoropyrimidine-irinotecan-based chemotherapy ± bevacizumab.
4. A baseline new tumor sample FFPE from a metastatic or primary site.
If the pt has an available tumor sample as an FFPE block with sufficient
material and has not received further anticancer treatment since sample
collection, a new tumor biopsy at baseline is not necessary. Archival
FFPE slides are not acceptable.Archival
tumor material is only acceptable if the patient has not
been treated with anti-EGFR or anti-human epidermal growth factor
receptor (HER)-2 therapies.
5 Amenable for biopsy
6 Measurable disease per RECIST 1.1
7.ECOG PS 0-1
8.Life expectancy = 12 weeks
9.LVEF = 50% by ECHO/MUGA
10 Adequat

Exclusion Criteria

1. CNSmetastases that are untreated or
symptomatic, or require radiation, surgery, or continued steroid therapy
to control symptoms within 14 days of study entry.
2. Known leptomeningeal involvement
3. Participation in another CT or treatment with any
investigational drug within 4 weeks prior to study entry
4. Any systemic anticancer therapy within 4 weeks or 5 half-lives,
whichever is shorter, of the first dose of study treatment. For cytotoxic
agents that have major delayed toxicity (eg, mitomycin C, nitrosoureas),
or anticancer immunotherapies, a washout period of 6 weeks is required.
5. Requirement for immunosuppressive medication
6. Major surgery or radiotherapy within 3 weeks of the first dose of
study treatment. Patients who received prior radiotherapy to =25% of
bone marrow are not eligible, irrespective of when it was received.
7. Persistent Grade >1 clinically significant toxicities related to prior
antineoplastic therapies (except for alopecia); stable sensory
neuropathy Grade =2 v4.03 is allowed.
8. History of hypersensitivity reaction to any of the excipients of
petosemtamab, human proteins, or any non-IMP treatment required for
this study
9. Uncontrolled hypertension (systolic [BP] >150 mmHg
and/or diastolic BP >100 mmHg) with appropriate treatment; unstable
angina; history of congestive heart failure of Class II-IV New York Heart
Association (NYHA) criteria, or serious cardiac arrhythmia requiring
treatment (except atrial fibrillation, paroxysmal supraventricular
tachycardia); or history of myocardial infarction within 6 months of
study entry
10. History of prior malignancies with the exception of excised cervical
intraepithelial neoplasia or nonmelanoma skin cancer, or curatively
treated cancer deemed at low risk for recurrence with no evidence of
disease for =3 years.
11. Current dyspnea at rest of any origin, or other diseases requiring
continuous oxygen therapy, including patients with a history of
interstitial lung disease (ILD) (eg, pneumonitis or pulmonary fibrosis),
or evidence of ILD on baseline chest computerized tomography (CT)
scan
12. Current serious illness or medical conditions including, but not
limited to, uncontrolled active infection, clinically significant pulmonary,
metabolic, or psychiatric disorders
13. Patients with known infectious diseases:
• Active hepatitis B infection without receiving antiviral treatment. Note:
o Patients who are HbsAg positive must receive antiviral treatment with
lamivudine, tenofovir, entecavir, or other antiviral agents, starting at
least =7 days before the initiation of study treatment.
o Patients with antecedents of hepatitis B (eg, anti-hepatitis B core
(anti-HBc) positive, HbsAg, and hepatitis B virus [HBV] DNA negative)
are eligible.
• Positive test for hepatitis C virus (HCV) RNA. Note: Patients in whom
HCV infection resolved spontaneously (ie, positive HCV antibodies
without detectable HCV RNA), or who achieved a sustained response
after antiviral treatment and show absence of detectable HCV RNA =6
months (with the use of interferon [IFN]-free regimens) or =12 months
(with the use of IFN-based regimens) after cessation of antiviral
treatment, are eligible.
14. Pregnant or breastfeeding patients; patients of childbearing potential
must use highly effective contraception methods prior to study entry, for
the duration of study participation, and for 6 months after the last dose
of petosemtamab.
15. 1L HNSCC combination cohort: has a diagnosis of immunodeficiency,
or

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified