Dose Escalation: Oral dose of RLY-1971 until Maximum Tolerated Dose (MTD), and Recommended Phase 2 dose (RP2D) are identified

Dose Expansion: Oral dose of RLY-1971 once Maximum Tolerated Dose (MTD), and Recommended Phase 2 Dose (RP2D) are identified.

RLY-1971

Clinical Trials

This study is a multi-center, open-label, dose escalation and expansion study of RLY-1971 in subjects with advanced or metastatic solid tumors.

Dose escalation/dose expansion study to assess the MTD, safety, tolerability, PK and preliminary anti-tumor activity of RLY-1971. Approximately 70 patients

RLY-1971 in Subjects With Advanced or Metastatic Solid Tumors

Phase 1, Open Label, Dose Escalation and Expansion Study of RLY-1971, a Highly Potent and Selective SHP2 Inhibitor, in Subjects With Advanced or Metastatic Solid Tumors

Blood will be collected at pre-dose at baseline on Cycle 1, Day 1 (C1D1) and at 3 time points (pre-dose, 2 hours post-dose, and 4 hours post-dose) on Cycle 1, Day 15 (C1D15) to assess the extent of target engagement

Blood will be collected at screening and at End of Treatment on all patients

DOR is defined as the time from the participant's initial objective response (CR or PR) to RLY-1971, to disease progression or death due to any cause, whichever occurs first

PFS is defined as the time from the start of study treatment to the first documented disease progression per RECIST v1.1, or death due to any cause, whichever occurs first

MTD is defined as a dose level immediately below that at which ≥2 of 6 subjects experience a DLT during the first cycle.

RP2D may be the same dose level or lower than the determined MTD.

Blood samples may be taken at pre-dose, 0.5, 1, 2, 4, 6, and 8hrs on Cycle 1 Day 1 and 15, 24 hrs post dose on Cycle 1 Day 2, and pre-dose on Cycle 2 Day 1

Evaluation by RECIST 1.1; ORR is defined as the proportion of subjects in the response evaluable population who achieve the best overall response (BOR) of CR or PR

DCR is defined as the percentage of response evaluable subjects who achieve a BOR of CR, PR or SD for at least 3 months

Hoffmann-La Roche

All Drugs and Chemicals

Antineoplastic Agents

Hematinics

Amino Acids

Antibodies

Cemiplimab

Antibodies, Bispecific

Immunoglobulins

Liver Extracts

Mitogens

Tyrosine Kinase Inhibitors

Antineoplastic Agents, Immunological

Tyrosine

Variety of mixed advanced solid tumor types

Head and Neck Squamous Cell Carcinoma (HNSCC)

Microsatellite Stable-Colorectal Cancer (MSS-CRC), with Active Liver Metastases and/or Active Peritoneal Metastases

MSS-CRC with Isolated Lung/Lymph Node Metastases (no active liver and no active peritoneal metastases)

Epidermal Growth Factor Receptor (EGFR) -mutant NSCLC Post Third Generation tyrosine kinase inhibitor (TKI)

EGFR-mutant NSCLC Post Third Generation TKI and Post Platinum-Doublet Chemotherapy

Intravenous (IV) infusion or subcutaneous (SC) injection will be administered every week (QW) or every 3 weeks (Q3W)

REGN7075

administered concomitantly Q3W by IV infusion or SC injection

cemiplimab

Platinum-based doublet chemotherapy

Clinical Trials Administrator

Clinical Trial Management

This study is researching an investigational drug called REGN7075 by itself and in combination with cemiplimab with or without chemotherapy. The study is focused on patients with certain solid tumors that are in an advanced stage. The aim of the study is to see how safe and tolerable REGN7075 is by itself and in combination with cemiplimab (with or without chemotherapy), and to find out what is the best dose of REGN7075 to be given to patients with advanced solid tumors when combined with cemiplimab (with or without chemotherapy). Another aim of the study is to see how effective REGN7075 by itself, or in combination with cemiplimab (with or without chemotherapy), is at treating cancer patients.

The study is also looking at:

* Side effects that may be experienced by people taking REGN7075 by itself and in combination with cemiplimab with or without chemotherapy.
* How REGN7075 works in the body by itself and in combination with cemiplimab with or without chemotherapy.
* How much REGN7075 is present in your blood when given by itself and in combination with cemiplimab with or without chemotherapy.
* To see if REGN7075 by itself and in combination with cemiplimab with or without chemotherapy works to treat your cancer by controlling the proliferation of tumor cells to shrink your tumor.

A Trial to Find Out How Safe REGN7075 is and How Well it Works in Combination With Cemiplimab for Adult Participants With Advanced Cancers

A Phase 1/2 Study of REGN7075 (EGFRxCD28 Costimulatory Bispecific Antibody) in Combination With Cemiplimab in Patients With Advanced Solid Tumors

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.

The EORTC QLQ CR-29 questionnaire consists of 29 items (Likert scale), with a response scale for each of them from 1 to 4, with the following structure: 1 = Not at All 2 = A little; 3 = Quite a Bit; 4 = Very much. The QLQ-CR29 has five functional and 18 symptom scales. It contains four subscales (urinary frequency (UF), blood and mucus in stool (BMS), stool frequency (SF), and body image (BI)) and 19 single items (urinary incontinence, dysuria, abdominal pain, buttock pain, bloating, dry mouth, hair loss, taste, anxiety, weight, flatulence, fecal incontinence, sore skin, embarrassment, stoma care problems, sexual interest (men), impotence, sexual interest (women), and dyspareunia). Scores can be linearly transformed to provide a score from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales.

The EORTC-QLQ-BR23 includes functional scales (body image, sexual functioning, sexual enjoyment, and future perspective) and single item symptoms scales (systemic therapy side effects, breast symptoms, arm symptoms, and upset by hair loss). Questions use 4-point Likert scale (1 'Not at All' to 4 'Very Much'). Scores average and transformed to 0-100 scale. High score for functional scale=high/healthy level of functioning. High score for single item=high level of symptomatology/problems.

The EORTC QLQ-LC13 is a 13-item, disease-specific module which assesses quality of life across multiple scales, including dyspnea, cough and chest pain.

The scale for EORTC-QLQ-LC13 is 1-4 for most outcome measures of systems, with 1 rated as "not at all" and 4 rated as "very much".

The EORTC QLQ-HN35 is a 35-item, disease-specific module which assesses quality of life across multiple scales, including pain, swallowing, and senses.

The questionnaire has 35 Likert type questions in total and the evaluation is made by giving the score of None: 1, A little: 2, Quite: 3, A lot: 4.

The EQ-5D-5L consists of EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.

The EORTC QLQ CR-29 questionnaire consists of 29 items (Likert scale), with a response scale for each of them from 1 to 4, with the following structure: 1 = Not at All 2 = A little; 3 = Quite a Bit; 4 = Very much. The QLQ-CR29 has five functional and 18 symptom scales. It contains four subscales (urinary frequency (UF), blood and mucus in stool (BMS), stool frequency (SF), and body image (BI)) and 19 single items (urinary incontinence, dysuria, abdominal pain, buttock pain, bloating, dry mouth, hair loss, taste, anxiety, weight, flatulence, fecal incontinence, sore skin, embarrassment, stoma care problems, sexual interest (men), impotence, sexual interest (women), and dyspareunia). . Scores can be linearly transformed to provide a score from 0 to 100. Higher scores represent better functioning on the functional scales and a higher level of symptoms on the symptom scales.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
RLY-1971 in Subjects With Advanced or Metastatic Solid Tumors	NCT04252339	Solid Tumor, Un...	RLY-1971	18 Years -	Hoffmann-La Roche
A Trial to Find Out How Safe REGN7075 is and How Well it Works in Combination With Cemiplimab for Adult Participants With Advanced Cancers	NCT04626635	Advanced Solid ...	REGN7075 cemiplimab Platinum-based ...	18 Years -	Regeneron Pharmaceuticals
RLY-1971 in Subjects With Advanced or Metastatic Solid Tumors	NCT04252339	Solid Tumor, Un...	RLY-1971	18 Years -	Hoffmann-La Roche
RLY-1971 in Subjects With Advanced or Metastatic Solid Tumors	NCT04252339	Solid Tumor, Un...	RLY-1971	18 Years -	Hoffmann-La Roche
A Trial to Find Out How Safe REGN7075 is and How Well it Works in Combination With Cemiplimab for Adult Participants With Advanced Cancers	NCT04626635	Advanced Solid ...	REGN7075 cemiplimab Platinum-based ...	18 Years -	Regeneron Pharmaceuticals

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